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457 results on '"Lynch, Thomas J."'

8. Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

Author

Sun, Xingshen, Olivier, Alicia K., Yi, Yaling, Pope, Christopher E., Hayden, Hillary S., Liang, Bo, Sui, Hongshu, Zhou, Weihong, Hager, Kyle R., Zhang, Yulong, Liu, Xiaoming, Yan, Ziying, Fisher, John T., Keiser, Nicholas W., Song, Yi, Tyler, Scott R., Goeken, J. Adam, Kinyon, Joann M., Radey, Matthew C., Fligg, Danielle, Wang, Xiaoyan, Xie, Weiliang, Lynch, Thomas J., Kaminsky, Paul M., Brittnacher, Mitchell J., Miller, Samuel I., Parekh, Kalpaj, Meyerholz, David K., Hoffman, Lucas R., Frana, Timothy, Stewart, Zoe A., and Engelhardt, John F.

Published
2014
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9. Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia.

Author

Pai, Albert C., Swatek, Anthony M., Lynch, Thomas J., Ahlers, Bethany A., Ievlev, Vitaly, Engelhardt, John F., and Parekh, Kalpaj R.

Subjects
VASCULAR endothelial growth factors, FERRET, BIOENGINEERING, EPITHELIUM, BRIDGE defects, TRACHEA
Abstract

Tracheal grafts may be necessary to bridge long-segment defects after curative resection for airway obstructions. Bioengineered grafts have emerged as an appealing option, given the possibilities of altering the histologic and cellular profile of the conduit. We previously designed a bioreactor capable of luminally decellularizing and recellularizing a ferret trachea with surface airway epithelia (SAE) basal cells (BCs), and we sought to assess the fate of these grafts when transplanted in an orthotopic fashion. As adjuncts to the procedure, we investigated the use of a vascular endothelial growth factor (VEGF)-laden hydrogel and of immunosuppression (IS) in graft revascularization and viability. IS was shown to limit early graft revascularization, but this effect could be counteracted with VEGF supplementation. Submucosal gland (SMG) loss was shown to be inevitable regardless of the revascularization strategy. Lastly, the bioengineered tracheas survived one month after transplant with differentiation of our implanted BCs that then transitioned into a recipient-derived functional epithelium. The work presented in this manuscript has important implications for future cellular and regenerative therapies. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Phase 1-2a Multicenter Dose-Ranging Study of Canfosfamide in Combination with Carboplatin and Paclitaxel as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer

Author

Sequist, Lecia V., Fidias, Panos M., Temel, Jennifer S., Kolevska, Tatjana, Rabin, Michael S., Boccia, Ralph V., Burris, Howard A., Belt, Robert J., Huberman, Mark S., Melnyk, Ostap, Mills, Glenn M., Englund, Craig W., Caldwell, David C., Keck, James G., Meng, Lisa, Jones, Marsha, Brown, Gail L., Edelman, Martin J., and Lynch, Thomas J.

Published
2009
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23. CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice

Author

Xie, Weiliang, Fisher, John T., Lynch, Thomas J., Luo, Meihui, Evans, Turan I.A., Neff, Traci L., Zhou, Weihong, Zhang, Yulong, Ou, Yi, Bunnett, Nigel W., Russo, Andrew F., Goodheart, Michael J., Parekh, Kalpaj R., Liu, Xiaoming, and Engelhardt, John F.

Subjects
Cystic fibrosis -- Development and progression -- Research -- Genetic aspects, Cellular signal transduction -- Research, Peptides -- Health aspects -- Physiological aspects -- Research, Health care industry
Abstract

In cystic fibrosis (CF), a lack of functional CF transmembrane conductance regulator (CFTR) chloride channels causes defective secretion by submucosal glands (SM[G.sub.s]), leading to persistent bacterial infection that damages airways and necessitates tissue repair. SM[G.sub.s] are also important niches for slow-cycling progenitor cells (SCP[C.sub.s]) in the proximal airways, which may be involved in disease-related airway repair. Here, we report that calcitonin generelated peptide (CGRP) activates CFTR-dependent SMG secretions and that this signaling pathway is hyperactivated in CF human, pig, ferret, and mouse SM[G.sub.s]. Since CGRP-expressing neuroendocrine cells reside in bronchiolar SCPC niches, we hypothesized that the glandular SCPC niche may be dysfunctional in CF. Consistent with this hypothesis, CFTR-deficient mice failed to maintain glandular SCP[C.sub.s] following airway injury. In wild-type mice, CGRP levels increased following airway injury and functioned as an injury-induced mitogen that stimulated SMG progenitor cell proliferation in vivo and altered the proliferative potential of airway progenitors in vitro. Components of the receptor for CGRP (RAMP1 and CLR) were expressed in a very small subset of SCP[C.sub.s], suggesting that CGRP indirectly stimulates SCPC proliferation in a non-cell-autonomous manner. These findings demonstrate that CGRP-dependent pathways for CFTR activation are abnormally upregulated in CF SM[G.sub.s] and that this sustained mitogenic signal alters properties of the SMG progenitor cell niche in CF airways. This discovery may have important implications for injury/repair mechanisms in the CF airway., Introduction Stem cell niches in adult organs play important roles in maintaining organ integrity in the setting of normal cellular turnover and injury. These microenvironments are unique and control intrinsic [...]

Published
2011
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27. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer

Author

Kwak, Eunice L., Ynng-Jue Bang, Camidge, D. Ross, Shaw, Alice T., Solomon, Benjamin, Maki, Robert G., Sai-Hong I. Ou, Dezube, Bruce J., Janne, Pasi A., Costa, Daniel B., Varella-Garcia, Marileila, Woo-Ho Kim, Lynch, Thomas J., Fidias, Panos, Stubbs, Hannah, Engelman, Jeffrey A., Sequist, Lecia V., WeiWei Tan, Gandhi, Leena, Mino-Kenudson, Mari, Wei, Greg C., Shreeve, S. Martin, Ratain, Mark J., Settleman, Jeffrey, Christensen, James G., Haber, Daniel A., Wilner, Keith, Salgia, Ravi, Shapiro, Geoffrey I., Clark, Jeffrey W., and Iafrate, A. John

Subjects
Lung cancer, Small cell -- Genetic aspects, Lung cancer, Small cell -- Diagnosis, Lung cancer, Small cell -- Care and treatment, Tyrosine -- Health aspects, Phosphotransferases -- Health aspects
Abstract

A study was conducted to evaluate the therapeutic efficacy of inhibition of anaplastic lymphoma kinase (ALK) in the case of non-small-cell lung cancer tumors. Results indicated that such ALK inhibition was effective in shrinkage of the tumor and stable disease in the case of most patients.

Published
2010

28. Early palliative care for patients with metastatic non-small-cell lung cancer

Author

Temel, Jennifer S., Greer, Joseph A., Muzikansky, Alona, Gallagher, Emily R., Admane, Sonal, Jackson, Vicki A., Dahlin, Constance M., Blinderman, Craig D., Jacobsen, Juliet, Pirl, William F., Billings, J. Andrew, and Lynch, Thomas J.

Subjects
Lung cancer -- Care and treatment, Palliative treatment -- Health aspects, Palliative treatment -- Usage, Outcome and process assessment (Health Care)
Abstract

A study was conducted to evaluate the benefits of introducing early palliative care in the case of patients with metastatic non-small-cell lung cancer on outcomes and end of life care. Results indicated that early palliative care in the case of such patients resulted in improved outcomes as well as longer survival and better quality of life and mood.

Published
2010

29. Lung Phenotype of Juvenile and Adult Cystic Fibrosis Transmembrane Conductance Regulator-Knockout Ferrets

Author

Sun, Xingshen, Olivier, Alicia K., Liang, Bo, Yi, Yaling, Sui, Hongshu, Evans, Turan I. A., Zhang, Yulong, Zhou, Weihong, Tyler, Scott R., Fisher, John T., Keiser, Nicholas W., Liu, Xiaoming, Yan, Ziying, Song, Yi, Goeken, Adam J., Kinyon, Joann M., Fligg, Danielle, Wang, Xiaoyan, Xie, Weiliang, Lynch, Thomas J., Kaminsky, Paul M., Stewart, Zoe A., Pope, Marshall R., Frana, Timothy, Meyerholz, David K., Parekh, Kalpaj, and Engelhardt, John F.

Published
2014
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30. Sox9 and Lef1 Regulate the Fate and Behavior of Airway Glandular Progenitors in Response to Injury.

Author

Ievlev, Vitaly, Jensen-Cody, Chandler C, Lynch, Thomas J, Pai, Albert C, Park, Soo, Shahin, Weam, Wang, Kai, Parekh, Kalpaj R, and Engelhardt, John F

Subjects
SOX transcription factors, AIRWAY (Anatomy), SUBMUCOUS plexus, CYSTIC fibrosis, STEM cells, BUILDING evacuation, WOUNDS & injuries
Abstract

Cartilaginous airways of larger mammals and the mouse trachea contain at least 3 well-established stem cell compartments, including basal cells of the surface airway epithelium (SAE) and ductal and myoepithelial cells of the submucosal glands (SMG). Here we demonstrate that glandular Sox9-expressing progenitors capable of SAE repair decline with age in mice. Notably, Sox9-lineage glandular progenitors produced basal and ciliated cells in the SAE, but failed to produce secretory cells. Lef1 was required for glandular Sox9 lineage contribution to SAE repair, and its deletion significantly reduced proliferation following injury. By contrast, in vivo deletion of Sox9 enhanced proliferation of progenitors in both the SAE and SMG shortly following injury, but these progenitors failed to proliferate in vitro in the absence of Sox9, similar to that previously shown for Lef1 deletion. In cystic fibrosis ferret airways, Sox9 expression inversely correlated with Ki67 proliferative marker expression in SMG and the SAE. Using in vitro and ex vivo models, we demonstrate that Sox9 is extinguished as glandular progenitors exit ducts and proliferate on the airway surface and that Sox9 is required for migration and proper differentiation of SMG, but not surface airway, progenitors. We propose a model whereby Wnt/Lef1 and Sox9 signals differentially regulate the proliferative and migratory behavior of glandular progenitors, respectively. Graphical Abstract [ABSTRACT FROM AUTHOR]

Published
2022
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31. Detections of mutation in EGFR in circulating lung-cancer cells

Author

Maheswaran, Shyamala, Sequist, Lecia V., Nagrath, Sunitha, Ulkus, Lindsey, Brannigan, Brian, Collura, Chey V., Inserra, Elizabeth, Diederichs, Sven, Iafrate, A. John, Bell, Daphne W., Digumarthy, Subba, Muzikansky, Alona, Irimia, Daniel, Settleman, Jeffrey, Tompkins, Ronald G., Lynch, Thomas J., Toner, Mehmet, and Haber, Daniel A.

Subjects
Gene mutations -- Analysis, Lung cancer, Non-small cell -- Genetic aspects, Lung cancer, Non-small cell -- Care and treatment
Abstract

The efficacy of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non-small-cell lung cancer is studied. Results indicated that molecular analysis of patients with blood cancer showed the emergence of activating EGFR mutations in circulating tumor cells during therapy.

Published
2008

32. Case 26-2004: A 56-year-old woman with cough and a lung nodule

Author

Lynch, Thomas J., Wright, Cameron D., Choi, Noah C., Aquino, Suzanne L., and Mark, Eugene J.

Subjects
Women -- Health aspects, Lung cancer -- Diagnosis
Abstract

A case of 56-year-old woman, evaluated in the thoracic oncology clinic for treatment of non-small-cell lung cancer is described. The diagnosis, management and treatment of the disease are stated.

Published
2004

33. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitnib

Author

Lynch, Thomas J., Brannigan, Brian W., Bell, Daphne W., Harris, Patricia L., Sordella, Rafaella, Haserlat, Sara M., Gurubhagavatula, Sarada, Okimoto, Ross A., Supko, Jeffrey G., and Haluska, Frank G.

Subjects
Mutation (Biology) -- Analysis, Lung cancer, Non-small cell -- Drug therapy
Abstract

A study conducted to search for mutations in the epidermal growth factor receptor (EGFR) gene in primary tumors from patients with non-small-cell lung cancer. Screening for such mutations in lung cancers may identify patients with response to gefitinib, is presented.

Published
2004

34. Efficacy of gefitinib, and inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial

Author

Kris, Mark G., Natale, Ronald B., Herbst, Roy S., Lynch, Thomas J., Jr., Prager, Diane, Belani, Chandra P., Schiller, Joan H., Kelly, Karen, Spiridonidis, Harris, Sandler, Alan, Albain, Kathy S., Cella, David, Wolf, Michael K., Averbuch, Steven D., Ochs, Judith J., and Kay, Andrea C.

Subjects
AstraZeneca Pharmaceuticals L.P. -- Product information, Iressa (Medication) -- Evaluation, Pharmaceutical industry -- Product information, Lung cancer, Non-small cell -- Drug therapy
Abstract

The drug Iressa may improve symptoms and cause some tumor shrinkage in patients with non-small cell lung cancer, according to a study of 216 patients. Between one-third and one-half experienced an improvement in their symptoms, depending on which dose they received. In one-fifth of the patients, the drug caused the tumor to shrink at least 50%.

Published
2003

36. A Novel Bioreactor for Reconstitution of the Epithelium and Submucosal Glands in Decellularized Ferret Tracheas.

Author

Pai, Albert C., Lynch, Thomas J., Ahlers, Bethany A., Ievlev, Vitaly, Engelhardt, John F., and Parekh, Kalpaj R.

Subjects
*FERRET, *GLANDS, *EPITHELIUM, *CELL differentiation, *AIRWAY (Anatomy), *TRACHEA
Abstract

Tracheal grafts introduce the possibility to treat airway pathologies that require resection. While there has been success with engraftment of the surface airway epithelium (SAE) onto decellularized tracheas, there has been minimal advancement in regenerating the submucosal glands (SMGs). We designed a cost-effective open-system perfusion bioreactor to investigate the engraftment potential of ferret SAEs and murine myoepithelial cells (MECs) on a partly decellularized ferret trachea with the goal of creating a fully functional tracheal replacement. An air–liquid interface was also arranged by perfusing humidified air through the lumen of a recellularized conduit to induce differentiation. Our versatile bioreactor design was shown to support the successful partial decellularization and recellularization of ferret tracheas. The decellularized grafts maintained biomechanical integrity and chondrocyte viability, consistent with other publications. The scaffolds supported SAE basal cell engraftment, and early differentiation was observed once an air–liquid interface had been established. Lastly, MEC engraftment was sustained, with evidence of diffuse SMG reconstitution. This model will help shed light on SMG regeneration and basal cell differentiation in vitro for the development of fully functional tracheal grafts before transplantation. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine

Author

Dias-Santagata, Dora, Akhavanfard, Sara, David, Serena S., Vernovsky, Kathy, Kuhlmann, Georgiana, Boisvert, Susan L., Stubbs, Hannah, McDermott, Ultan, Settleman, Jeffrey, Kwak, Eunice L., Clark, Jeffrey W., Isakoff, Steven J., Sequist, Lecia V., Engelman, Jeffrey A., Lynch, Thomas J., Haber, Daniel A., Louis, David N., Ellisen, Leif W., Borger, Darrell R., and Iafrate, John A.

Published
2010
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