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4. Long‐Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model

Author

Balaji, Poornima, primary, Barry, Michael A., additional, Tran, Vu Toan, additional, Marschner, Simone, additional, Lu, Juntang, additional, Nguyen, Duc Minh, additional, Mina, Ashraf, additional, Bandodkar, Sushil, additional, Alvarez, Shirley, additional, James, Virginia, additional, Ronquillo, John, additional, Varikatt, Winny, additional, Kovoor, Pramesh, additional, McEwan, Alistair, additional, Thiagalingam, Aravinda, additional, Thomas, Stuart P., additional, and Qian, Pierre C., additional

Published
2024
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6. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Author

Allison, Sarah, Bailey, Peter J., Bailey, Ulla-Maja, Biankin, Andrew V., Beraldi, Dario, Brunton, Holly, Caligiuri, Giuseppina, Cameron, Euan, Chang, David K., Cooke, Susanna L., Cunningham, Richard, Dreyer, Stephan, Grimwood, Paul, Kelly, Shane, Lampraki, Eirini-Maria, Marshall, John, Martin, Sancha, McDade, Brian, McElroy, Daniel, Musgrove, Elizabeth A., Nourse, Craig, Paulus-Hock, Viola, Ramsay, Donna, Upstill-Goddard, Rosie, Wright, Derek, Jones, Marc D., Evers, Lisa, Rebus, Selma, Rahib, Lola, Serrels, Bryan, Hair, Jane, Jamieson, Nigel B., McKay, Colin J., Westwood, Paul, Williams, Nicola, Duthie, Fraser, Johns, Amber L., Mawson, Amanda, Scarlett, Christopher J., Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye H., Martyn-Smith, Mona, Thomas, Michelle T., Chantrill, Lorraine A., Chin, Venessa T., Chou, Angela, Cowley, Mark J., Humphris, Jeremy L., Mead, R. Scott, Nagrial, Adnan M., Pajic, Marina, Pettit, Jessica, Pinese, Mark, Rooman, Ilse, Wu, Jianmin, Tao, Jiang, DiPietro, Renee, Watson, Clare, Steinmann, Angela, Lee, Hong Ching, Wong, Rachel, Pinho, Andreia V., Giry-Laterriere, Marc, Daly, Roger J., Sutherland, Robert L., Grimmond, Sean M., Waddell, Nicola, Kassahn, Karin S., Miller, David K., Wilson, Peter J., Patch, Ann-Marie, Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Christina, Nones, Katia, Fink, J. Lynn, Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Newell, Felicity, Pearson, John V., Bailey, Peter, Quinn, Michael, Nagaraj, Shivashankar, Kazakoff, Stephen, Waddell, Nick, Krisnan, Keerthana, Quek, Kelly, Wood, David, Samra, Jaswinder S., Gill, Anthony J., Pavlakis, Nick, Guminski, Alex, Toon, Christopher, Asghari, Ray, Merrett, Neil D., Pavey, Darren, Das, Amitabha, Cosman, Peter H., Ismail, Kasim, O’Connnor, Chelsie, Lam, Vincent W., McLeod, Duncan, Pleass, Henry C., Richardson, Arthur, James, Virginia, Kench, James G., Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Zeps, Nikolajs, Beilin, Maria, Feeney, Kynan, Nguyen, Nan Q., Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, O’Rourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Mountain, Angela, Biobank, Victorian Cancer, Eshleman, James R., Hruban, Ralph H., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Schulick, Richard D., Wolfgang, Christopher L., Morgan, Richard A., Hodgin, Mary, Scarpa, Aldo, Lawlor, Rita T., Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Bassi, Claudio, Tempero, Margaret A., Graham, Janet S., Dreyer, Stephan B., Paris, Clara, Dray, Eloise, Plenker, Dennis, Galluzzo, Zachary, Tesson, Mathias, Jones, Marc, Moran-Jones, Kim, Wright, Derek W., Oien, Karin, McGregor, Grant A., Gulati, Aditi, Brough, Rachel, Bajrami, Ilirjana, Pettitt, Stephan, Dziubinski, Michele L., Candido, Juliana, Balkwill, Frances, Barry, Simon T., Grützmann, Robert, Johns, Amber, Froeling, Fieke E.M., Beer, Phillip, Petersen, Gloria M., Ashworth, Alan, Frame, Margaret C., Crawford, Howard C., Simeone, Diane M., Lord, Chris, Mukhopadhyay, Debabrata, Pilarsky, Christian, Tuveson, David A., Morton, Jennifer P., and Sansom, Owen J.

Published
2021
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8. Whole genomes redefine the mutational landscape of pancreatic cancer

Author

Biankin, Andrew V, Johns, Amber L, Mawson, Amanda, Chang, David K, Scarlett, Christopher J, Brancato, Mary-Anne L, Rowe, Sarah J, Simpson, Skye H, Martyn-Smith, Mona, Thomas, Michelle T, Chantrill, Lorraine A, Chin, Venessa T, Chou, Angela, Cowley, Mark J, Humphris, Jeremy L, Jones, Marc D, Scott Mead, R, Nagrial, Adnan M, Pajic, Marina, Pettit, Jessica, Pinese, Mark, Rooman, Ilse, Wu, Jianmin, Tao, Jiang, DiPietro, Renee, Watson, Clare, Steinmann, Angela, Ching Lee, Hong, Wong, Rachel, Pinho, Andreia V, Giry-Laterriere, Marc, Daly, Roger J, Musgrove, Elizabeth A, Sutherland, Robert L, Grimmond, Sean M, Waddell, Nicola, Kassahn, Karin S, Miller, David K, Wilson, Peter J, Patch, Ann-Marie, Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Christina, Nones, Katia, Lynn Fink, J, Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Newell, Felicity, Pearson, John V, Bailey, Peter, Quinn, Michael, Nagaraj, Shivashankar, Kazakoff, Stephen, Waddell, Nick, Krisnan, Keerthana, Quek, Kelly, Wood, David, Fadlullah, Muhammad ZH, Samra, Jaswinder S, Gill, Anthony J, Pavlakis, Nick, Guminski, Alex, Toon, Christopher, Asghari, Ray, Merrett, Neil D, Pavey, Darren, Das, Amitabha, Cosman, Peter H, Ismail, Kasim, O’Connnor, Chelsie, Lam Duncan McLeod, Vincent W, Pleass, Henry C, Richardson, Arthur, James, Virginia, Kench, James G, Cooper, Caroline L, Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forest, Cindy, Laycock, Andrew, Epari, Krishna P, Ballal, Mo, Fletcher, David R, Mukhedkar, Sanjay, and Spry, Nigel A

Subjects
Cancer, Human Genome, Pancreatic Cancer, Digestive Diseases, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Adenocarcinoma, Animals, Carcinoma, Pancreatic Ductal, DNA Mutational Analysis, DNA Repair, Female, Genes, BRCA1, Genes, BRCA2, Genetic Markers, Genome, Human, Genomic Instability, Genomics, Genotype, Humans, Mice, Mutation, Pancreatic Neoplasms, Platinum, Point Mutation, Poly(ADP-ribose) Polymerase Inhibitors, Xenograft Model Antitumor Assays, Australian Pancreatic Cancer Genome Initiative, General Science & Technology
Abstract

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Published
2015

11. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

Author

Miller, Timothy M, Cudkowicz, Merit E, Andrews, Jinsy A, Hesters, Adele, Kermorvant, Hugo, Lacomblez, Lucette, Forestier, Nadine Le, Lenglet, Thimotée, Retail, Maryvonne, Ruiz Del Mar Amador, Maria, Salachas, François, Shotar, Eimad, Sourour, Nader, Babu, Suma, Dorst, Johannes, Froehlich, Elke, Fromm, Andrea, Kandler, Katharina, Langer, Eva, Leichtle, Sarah, Ludolph, Albert, Mayer, Kristina, Michels, Sebastian, Raubold, Sabine, Benatar, Michael, Schuster, Joachim, Weiland, Ulrike, Wiesenfarth, Maximilian, Witzel, Simon, Calvo, Andrea, Canosa, Antonio, Casale, Federico, Chiò, Adriano, Fuda, Giuseppe, Grassano, Maurizio, McDermott, Christopher J, Marchese, Giulia, Moglia, Cristina, Palumbo, Francesca, Salamone, Paolina, Ajiki, Takahiro, Akasaka, Aya, Ando, Masahiro, Arata, Hitoshi, Asuka, Kitamura, Baba, Kosuke, Cochrane, Thos, Bekku, Goichi, Chiba, Tomoya, Date, Yugaku, Eriko, Takeuchi, Hashiguchi, Akihiro, Hatatori, Ritsuko, Hayano, Eri, Hayashi, Yuto, Higashi, Keiko, Higuchi, Eriko, Chary, Sowmya, Hiramatsu, Yu, Horikawa, Rui, Ikenaka, Kensuke, Ishiura, Hiroyuki, Ito, Daisuke, Kawai, Sachiko, Kikuchi, Junko, Kuzuyama, Haruko, Li, Xuehong, Matsumoto, Chika, Chew, Sheena, Matsuura, Eiji, Michizono, Kumiko, Mitsui, Jun, Mitsutake, Akihiko, Mochizuki, Hideki, Nagamatsu, Akemi, Nagano, Seiichi, Nakamura, Tomonori, Naruse, Hiroya, Ogasawara, Asuka, Zhu, Han, Okada, Kensuke, Okamoto, Yuji, Okuno, Tatsusada, Oyama, Satoshi, Ozono, Tatsuhiko, Sakiyama, Yusuke, Sakuishi, Kaori, Seki, Morinobu, Shibata, Shota, Shimizu, Mikito, Wu, Fan, Takahata, Katsunori, Takahito, Yoshizaki, Takashima, Hiroshi, Takeichi, Hiroko, Tashiro, Yuichi, Toda, Tatsushi, Tomizu, Yuki, Tomoya, Wadayama, Ujiakira, Nishiike, Yashita, Daiki, Nestorov, Ivan, Al-Chalabi, Ammar, Alix, James, Bangalore, Priyadarshini, Blackburn, Daniel, Chiwera, Theresa, Clegg, Rosie, Collins, Alexis, Cooper-Knock, Jonathan, Emery, Anna, Franklin, John, Genge, Angela, Graham, Danielle, Green, Louisa, Harvey, Callum, Hobson, Esther, Islam, Mahjabim, Jenkins, Thomas Michael, Kazoka, Mbombe, Kelly, Gillian, Korley, Mercy, Madarshahaian, Daniel, Mayl, Keith, Sun, Peng, McDermott, Christopher John, Radford, Alex, Shaw, Christopher, Shaw, Pamela J, Sidebottom, Joe, Smart, Lynne, Sreedharan, Jemeen, Stone, Ben, Tsironis, Theocharis, Tuddenham, Lee, McNeill, Manjit, Verber, Nick, Wollff, Helen, Young, Stacy, Zis, Panagiotis, Adamo, Ashley, Ahmed, Arubah, Ajroud-Driss, Senda, Alameda, Gustave, Arcila-Londono, Ximena, Fanning, Laura, Baird, Candy, Bazan, Tracy, Berry, James, Bordeau, Jane, Bradford, Wendy, Brook, Nyda, Brown, Lauren, Bucelli, Robert C, Ferguson, Toby A, Buckner, Katherine, Budler, Michael W, Burba, Lindita, Burke, Katherine, Calhoun, Ashley D, Campbell, Sarah, Carey, Judith, Caristo, Irys B, Carty, Simon, Chan, Emmanuel, Fradette, Stephanie, Chaudhry, Vinay, Chen, Ricky, Chow, Saephanh, Clawson, Lora L, Clemens, Mitchell, Cloninger, Suzann E, Coleman-Wood, Krista, Cooper, Thomas N, Cummings, Arlena, Daniels, Jacquelyn, VALOR, DeSaro, Pamela, DeWitt, Michelle, Dedi, Brixhilda, Dempsey, Debbie, Denny, Carol, Doherty, Jenna, Doherty, Leana, Donahue, Megan, Doyle, Michael, Duncan, Jessie, Group, OLE Working, Elman, Lauren, Eloge, Christine M, Echiti, Desirae R, Ferrey, Dominic, Fournier, Christina, Fukumura, Yuriko, Gallagher, Katherine, Garaycoa, Jessica, Garrett, Mark, Gibson, Richard L, Beullens, Lien, Gifford, Ryan, Glass, Jonathan D, Gogol, Danuta, Golden, Shea, Gonzalez, Alexa, Goodman, Ira, Goolsby, Christopher, Goslin, Kimberly, Goulbourne, Michael, Granit, Volkan, Claeys, Kristl, Grignon, Anne-Laure, GuhaRay, Adreeja, Guide, Debra, Gundogdu, Melek Betul, Gutierrez, Gil, Hastings, Debbie, Hayzen, Colleen, Herzog, Hilary, Holloway, Raegan, Jacobs, Gabriel, Claeys, Thomas, Jacobsen, Bill, James, Virginia, Jenkins, Liberty, Jockel-Balsarotti, Jennifer, Johnson, Linda Carol, Jose, Sunil, Joslin, Benjamin, Karanja, Elizabeth, Katz, Jonathan, Keener, Anthony, Couwelier, Goedele, Kittle, Gale, Klein, Sara, Kreple, Collin, Rebecca, Rebecca, Kuenzler, Kuenzler, Kusnir, Jorge, Labbe, Kristen, Lachica-Encinas, Nicolet, Ladha, Shafeeq, Leimer, Lesli, D'Hondt, Ann, Levy, Michael, Levy, Wendy, Li, Yingji, Likanje, Marie-France, Livigni, Rebecca, Locatelli, Eduardo, Luppino, Sarah, Malcolm, Amber, Maragakis, Nicholas, Marin, Horia, Debien, Elisa, Markowitz, Clyde, Markway, Jesse, McCaffrey, Alexandra, McCoy, Arita, McCoy Gross, Kelly, Mehta, Kush, Meyer, Robert, Milan, Jennifer, Miller, Timothy, Miller, Robert G, de Keersmaecker, Sebastiaan, Morales, Francisco, Mosmiller, Elizabeth, Mott, Donovan, Moulton, Kelsey, Murphy, Christine A, Negron, Tirso, Nelson, Cassandra, Newman, Daniel S, Nissinen, Janne Kristoffer, Norman, Andrew, Della Faille, Laetitia, Ohkubo, Takuya, Olney, Nicholas, Ortiz, Natasha, Oskarsson, Bjorn, Pace, Mitchell, Packard, Kathleen, Padgett, Denny, Paganoni, Sabrina, Paredes, Maria E, Parker, Elizabeth, Delmotte, Koen, Partlow, Ann, Pattee, Gary L, Paulett, Jany, Pelot, Antoinette, Pfeifer, Kyle M, Pijanowski, Olivia, Pioro, Erik, Polak, Meraida, Prakash, Ahalya, Previte, Rosemarie, Depoortere, Sofie, Pukenas, Bryan, Quinn, Colin, Ravits, John, Razavi, Ryan, Regan, Tyler, Riley, Kristen M, Roth, Heather, Sanders, Danica, Scalia, Jennifer, Schmidt, Emma, de Velder, Laura, Schwen, Edward, Shah, Jaimin, Shah, Stuti, Shefner, Jeremy, Sheldon, Danielle, Simmons, Karon, Singh, Navneet K, Singleton, Jessica, Smiley, Richard, Smith, William B, Dobbels, Laurens, Smith, Sean, Sotirchos, Elias, Sorenson, Eric, Staff, Nathan, Steele, Julie, Steijlen, Kara, Stirrat, Taylor, Stoica, George S, Strong, Stephanie, Sufit, Robert, Sobue, Gen, Gijs, Jeroen, Sultze, Jane, Swartz, Amy, Szymanski, April, Tay, Anna, Thakore, Nimish, Thiessen, Diana, Thotala, Sukrutha, Trudell, Randall G, Turcotte, Nicole, Turner, Michelle, Horckmans, Simon, Uchil, Alpa, Upadhyay, Vihar, Usman, Uzma, Vallis, Anne, Vaporean-Bussey, Danielle, Vladimirova, Valentine, Weber, Harli, Winbigler, Jennifer, Wojanowski, Heather, Wulf, Charlie, Lamaire, Nikita, Yasek, Julia, Yoo, Stephanie, Zivalic, Hannah, Cole, Alexandra, File, Greta, Foate, Jeremy, Mason, Deborah, Newton, Susan, Roberts, Stephen, Sellwood, Cory Dean, Liessens, Hannelore, Swan, James, Werno, Anja, Zhong, Cathy, Masrori, Pegah, Nysten, Celine, Schotte, Caroline, Serrien, Anouk, Swinnen, Bart, Tilkin, Petra, van Daele, Sien, Van Damme, Philip, Vynckier, Jan, Wouters, Anke, Abrahao, Agessandro, Angle, Mark, Badawy, Mohamed, Berube, Maxime, Bertone, Vanessa, Cooper, Sarah Marie, Dobrowolski, Peter, Fong, Helen, Hannouche, Matthew, Hartley, Denise, Hogan, Michael, Johnston, Wendy, Khalfallah, Yousra, Korngut, Lawrence, Kroetsch, Gina, Letourneau, Justin, Magnussen, Claire, Martinez, Jose, Massie, Rami, Mobach, Theodore, Mookshah, Jahan, Ozelsel, Timur, Parks, Andrea, Petrillo, Janet, Pfeffer, Gerald, Ludolph, Albert C, Pham, Shirley, Phung, Liane, Shiungsun, Rodney, Pi-Shan, Li, Santos, Denizart, Salmon, Kristiana, Saunders, Natalie, Sembinelli, Dylan, Tymkow, Kelsey, Wong, Berchman, Zinman, Lorne, Karlsborg, Merete, Pedersen Lomholt, Therese, Nilsson, Sigrid, Salvesen, Lisette, Skov, Pernille, Svenstrup, Kristen, Bruneteau, Gaelle, Calerencon, Frederic, and Guimaraes Costa, Raquel

Subjects
Adult, drug effects [Recovery of Function], Spinal, Oligonucleotides, blood [Neurofilament Proteins], administration & dosage [Oligonucleotides, Antisense], tofersen, Injections, blood [Amyotrophic Lateral Sclerosis], pharmacology [Oligonucleotides, Antisense], Superoxide Dismutase-1, Double-Blind Method, Neurofilament Proteins, Humans, ddc:610, Antisense, Injections, Spinal, Biomarkers, Recovery of Function, Amyotrophic Lateral Sclerosis, Oligonucleotides, Antisense, blood [Biomarkers], drug therapy [Amyotrophic Lateral Sclerosis], therapeutic use [Oligonucleotides, Antisense], SOD1 protein, human, General Medicine, genetics [Superoxide Dismutase-1], genetics [Amyotrophic Lateral Sclerosis], cerebrospinal fluid [Biomarkers], cerebrospinal fluid [Superoxide Dismutase-1], cerebrospinal fluid [Amyotrophic Lateral Sclerosis]
Abstract

The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort).A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).

Published
2022

12. Association of macrophage phenotypes with atherosclerotic plaque complex features

Author

James, Virginia

Subjects
macrophage phenotypes, advanced plaque and association with complex features, Atherosclerosis, take-up of lipid
Abstract

Background: Cardiovascular disease (CVD) remains a leading cause of mortality and morbidity globally. Atherosclerosis is the main underlying cause of the major cardiovascular clinical events of heart attack and stroke. Atherosclerosis is a chronic inflammatory and lipid (oxLDL) driven disease initiated by endothelial injury, subsequent dysfunction, and immune activation, resulting in an inflammatory reaction followed by lipoprotein accumulation and deposition. Clinically significant is the vulnerable or unstable plaque morphology, as its unpredictable progression can often lead to rupture and subsequent thrombosis, manifesting as myocardial infarction (MI) or stroke. The stability of advanced plaques is therefore a key determining factor in the clinical outcome of cardiovascular disease. The composition of the atherosclerotic plaque is the most important determining factor, especially the size of the lipid core and the thickness and strength of the overlying protective cap. Monocyte derived macrophages play a pivotal role in all aspects of atherogenesis, from initiation to progression. Although there is a spectrum of macrophages involved in atherosclerosis, macrophages have been divided into two main contrasting groups, the classically activated M1 macrophages, and the alternatively activated M2 macrophages. Macrophages have been shown to have remarkable plasticity influenced by the local microenvironment. It is well known that heterogenous M1 and M2 macrophages are involved in all stages of atherosclerotic plaque development, however greater understanding of their role in plaque stability is needed. Classically activated M1 macrophages are designated as inflammatory, atherogenic and associated with core formation, cap degradation and plaque progression, thereby promoting instability, whereas alternatively M2 macrophages are defined as anti-inflammatory, anti-atherogenic, angiogenic wound healing and promote plaque stability. The prevalence and distribution of M1 and M2 macrophages subsets is thought to differ and hence influence the stability of the plaque. Foam cells taking up lipid are also a major contributor to atherosclerotic plaque development and destabilisation of the plaque, due to their formation of a lipid pool and enlargement of the necrotic core. Though whether foam cells are involved in other aspects of stability remains to be seen. The current consensus suggests that the conversion or differentiation of plaque monocytes into an M2 phenotype would be beneficial to reduce inflammation and increase collagen production, thereby stabilising and regressing the plaque. However, this view is over-simplified and requires further exploration. Aims: To examine the distribution of M1 and M2 macrophage subsets, and their foam cell forms, in early and advanced atherosclerotic plaques. Specifically, within the major morphological regions of the plaque and their associations with complex compositional contents, to give insight into their influence on the stability of the plaque. Methods: A total of 20 surgically excised carotid endarterectomy (CEA) ex-vivo plaques were examined. Histochemical and immuno staining were performed, and high-resolution digital images were examined. The haematoxylin and eosin (H&E) stain was used to grade and classify the plaques and CD68+ve staining identified macrophage rich areas. M1 (CD86) and M2 (CD163 and CD206) macrophage marker stains were used to identify macrophage subsets. Double immuno-staining with adipophilin differentiated related protein (ADRP), a marker for lipid was used to identify foam cells actively taking up lipid. Plaque compositional features including, calcium, microvessels, cholesterol crystals and haemorrhage, were detected with special stains. Examining macrophage distribution in relation to these compositional features, and importantly, any phenotype differences, was used to infer their influence on plaque stability. Results: Our findings have shown macrophages are distributed throughout the plaques major morphological features, displaying a similar distribution pattern. In the cap, M1 and M2 macrophage subsets adopted a spindle shape morphology. These spindle shaped macrophage have the ability to accumulate variable amounts of lipid, a feature that may have been overlooked previously. Further, rather than the shape being a function of M1 or M2 phenotype, we found that cap macrophages are restricted in size due to the fibrous microenvironment. M1 and M2 foam cells, both those taking up lipid (ADRP+ve) and not currently taking up lipid (ADRP-ve), were well distributed throughout the core, but also found distant to the core, and appeared to be taking up similar amounts of lipid. Rather than finding any differences between the subsets, we observed similar distribution and lipid accumulation capability. This may suggest that both M1 and M2 subsets may influence plaque stability through their presence in the cap and the core. Investigating the compositional features of advanced plaques, including early and late calcification with M1 and M2 subsets, our findings suggest no difference in association of the subsets with calcium, as only small numbers were observed to be colocalised with calcium deposits. Further M1 and M2 macrophages often colocalised with microvessel walls, however foam cell subsets were rarely found colocating with the microvessel walls, these similarities in colocalisation do not support the view of M1 as pro-inflammatory and M2 as anti-inflammatory, in relation to the destabilising feature of microvessels. This study also reported that both M1 and M2 macrophages and foam cells are associated with cholesterol crystals, as they were commonly colocalised with cholesterol crystals in plaque samples. Our findings of the colocalisation of M2 subsets is surprising as cholesterol crystals are thought to trigger the inflammasome pathway, which has been shown to promote a pro-inflammatory M1 phenotype. Further, our study reported that a haemorrhagic environment is not associated with only M2 macrophages, as we observed the expression of M1 (CD86+ve) and M2 (CD163+ve) macrophages and foam cells in haemorrhagic regions. Our findings disagree with previous studies that found M2 markers (CD206+ve and CD163+ve) to be more prevalent in areas of prior haemorrhage, in comparison to M1 markers. We took this further and found both M1 and M2 macrophages and foam cells were located in early plaque, pathological intimal thickening (PIT) sections and had the capacity to actively take up lipid. Analysis of PIT samples therefore allowed us to observe the initial state of M1 and M2 subsets before the influence of complex microenvironmental features, suggesting their presence and function is not solely determined by the complex feature of haemorrhage. We also asked whether the activating transcription factor -1 (ATF-1) can be used to distinguish between M2 ADRP-ve foam cells, and M2 ADRP+ve foam cells, i.e., delineate between M2 and haemorrhage-specialist macrophages (Mhem), as ATF-1 is proposed to be a specific marker that directs the differentiation of Mhem macrophages in haemorrhagic regions, making them resistant to taking up lipid. However, we found Mhem cells cannot be distinguished from M2 foam cells by ATF-1+ve expression, as we observed ADRP+ve cells with positive ATF-1 staining, which challenges the current literature. In fact, we found ATF-1+ve widely distributed throughout advanced and PIT plaques, not restricted to haemorrhagic regions. We then performed iron staining to reveal the age of the haemorrhage within the plaque as the microenvironment may influence lipid or iron accumulation by M2 macrophages. Considering we saw ATF-1+ve/ ADRP +ve co-expression in foam cells in early haemorrhagic regions (Glycophorin A +ve stained), and ATF-1+ve/ADRP+ve co-expression in late haemorrhagic regions (Perl’s stained), we suggest that ATF-1+ve expression does not restrict the taking up of lipid function of macrophages, however in later ages of the plaque, may be involved in promoting iron accumulation. Conclusion: We provide evidence that in advanced and early PIT plaques M1 and M2 macrophage subsets are similarly localised throughout the plaque, both performing the crucial function of taking up lipid. M2 subsets are likely to be associated with complex plaque features that induce instability, furthermore, they are not restricted to haemorrhagic microenvironments. Our data may help us better understand the diversity and complexity of the roles of M1 and M2 subsets interacting with specific complex plaque components, including calcium, microvessels, cholesterol crystals and haemorrhage, within advanced atherosclerotic plaques. This study provides evidence that rather than functional differences between M1 and M2 macrophages, instead there are similarities in distribution and the capacity of taking up lipid. Therefore, targeting one macrophage phenotype within the dynamic plaque microenvironment may not be beneficial as thought to stabilise and regress atherosclerotic plaques.

Published
2023

16. Nanohydrophobic Interaction Chromatography Coupled to Ultraviolet Photodissociation Mass Spectrometry for the Analysis of Intact Proteins in Low Charge States

Author

Blevins, Molly S., primary, Juetten, Kyle J., additional, James, Virginia K., additional, Butalewicz, Jamie P., additional, Escobar, Edwin E., additional, Lanzillotti, Michael B., additional, Sanders, James D., additional, Fort, Kyle L., additional, and Brodbelt, Jennifer S., additional

Published
2022
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17. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Author

Balachandran, Vinod P., Łuksza, Marta, Zhao, Julia N., Makarov, Vladimir, Moral, John Alec, Remark, Romain, Herbst, Brian, Askan, Gokce, Bhanot, Umesh, Senbabaoglu, Yasin, Wells, Daniel K., Ormsby Cary, Charles Ian, Grbovic-Huezo, Olivera, Attiyeh, Marc, Medina, Benjamin, Zhang, Jennifer, Loo, Jennifer, Saglimbeni, Joseph, Abu-Akeel, Mohsen, Zappasodi, Roberta, Riaz, Nadeem, Smoragiewicz, Martin, Kelley, Larkin Z., Basturk, Olca, Johns, Amber L., Mead, Scott R., Gill, Anthony J., Chang, David K., McKay, Skye H., Chantrill, Lorraine A., Chin, Venessa T., Chou, Angela, Humphris, Jeremy L., Pajic, Marina, Steinmann, Angela, Arshi, Mehreen, Drury, Ali, Froio, Danielle, Morgan, Ashleigh, Timpson, Paul, Hermann, David, Vennin, Claire, Warren, Sean, Pinese, Mark, Wu, Jianmin, Pinho, Andreia V., Tucker, Katherine, Andrews, Lesley, Samra, Jaswinder S., Arena, Jennifer, Pavlakis, Nick, High, Hilda A., Mittal, Anubhav, Biankin, Andrew V., Bailey, Peter, Martin, Sancha, Musgrove, Elizabeth A., Jones, Marc D., Nourse, Craig, Jamieson, Nigel B., Stoita, Alina, Williams, David, Spigelman, Allan, Waddell, Nicola, Pearson, John V., Patch, Ann-Marie, Nones, Katia, Newell, Felicity, Mukhopadhyay, Pamela, Addala, Venkateswar, Kazakoff, Stephen, Holmes, Oliver, Leonard, Conrad, Wood, Scott, Xu, Christina, Grimmond, Sean M., Hofmann, Oliver, Wilson, Peter J., Christ, Angelika, Bruxner, Tim, Asghari, Ray, Merrett, Neil D., Pavey, Darren, Das, Amitabha, Goodwin, Annabel, Cosman, Peter H., Ismail, Kasim, O’Connor, Chelsie, Cooper, Caroline L., Grimison, Peter, Kench, James G., Sandroussi, Charbel, Lam, Vincent W., McLeod, Duncan, Nagrial, Adnan M., Kirk, Judy, James, Virginia, Texler, Michael, Forest, Cindy, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Zeps, Nikolajs, Beilin, Maria, Feeney, Kynan, Nguyen, Nan Q., Ruszkiewicz, Andrew R., Worthley, Chris, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Clouston, Andrew D., Martin, Patrick, Barbour, Andrew P., O’Rourke, Thomas J., Fawcett, Jonathan W., Slater, Kellee, Hatzifotis, Michael, Hodgkinson, Peter, Nikfarjam, Mehrdad, Eshleman, James R., Hruban, Ralph H., Wolfgang, Christopher L., Hodgin, Mary, Scarpa, Aldo, Lawlor, Rita T., Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Bassi, Claudio, Gönen, Mithat, Levine, Arnold J., Allen, Peter J., Fearon, Douglas T., Merad, Miriam, Gnjatic, Sacha, Iacobuzio-Donahue, Christine A., Wolchok, Jedd D., DeMatteo, Ronald P., Chan, Timothy A., Greenbaum, Benjamin D., Merghoub, Taha, and Leach, Steven D.

Published
2017
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18. Clinically meaningful change: evaluation of the Rasch-built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) and the ALSFRS-R.

Author

Fournier, Christina N., James, Virginia, and Glass, Jonathan D.

Subjects
*AMYOTROPHIC lateral sclerosis, *DETECTION limit, *MEASUREMENT errors, *DISABILITIES, *STANDARD deviations
Abstract

To investigate clinically meaningful change for ROADS and ALSFRS-R using a patient-defined approach. Data were reviewed from participants assessed at the Emory ALS Center from 2019–2022 with two assessments using both ROADS and ALSFRS-R and a completed patient-reported global impression of change scale at the second visit. Minimal important difference (MID), or the smallest amount of change that is clinically relevant, was assessed based on patient reported impression of change for ROADS and ALSFRS-R. Minimal detectable change (MDC), the smallest amount of change exceeding the threshold for measurement error, was assessed for ROADS and ALSFRS-R using standard deviations for participants self-rated as "unchanged". Data were included from 162 participants. For ROADS (total possible normed score = 146), MID = 5.81 and MDC = 2.83 points. For ALSFRS-R (total possible sum-score = 48), MID = 3.24 and MDC = 1.59 points. Clinically meaningful decline during the assessment period was observed in 98/162 (60.49%) participants on ROADS and 75/162 (46.30) participants on ALSFRS-R (OR = 1.63, 95% CI [1.0009, 2.66]). Changes that are on average less than 5.81 points (3.98%) on the normed ROADS score or less than 3.24 points (6.75%) on the ALSFRS-R sum-score may not be clinically meaningful according to a patient-defined approach. Understanding the clinical and statistical limitations of these scales is crucial when designing and interpreting ALS research studies. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Enhanced Ion Mobility Separation and Characterization of Isomeric Phosphatidylcholines Using Absorption Mode Fourier Transform Multiplexing and Ultraviolet Photodissociation Mass Spectrometry

Author

Sanders, James D., primary, Shields, Samuel W., additional, Escobar, Edwin E., additional, Lanzillotti, Michael B., additional, Butalewicz, Jamie P., additional, James, Virginia K., additional, Blevins, Molly S., additional, Sipe, Sarah N., additional, and Brodbelt, Jennifer S., additional

Published
2022
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20. Whole genomes redefine the mutational landscape of pancreatic cancer

Author

Waddell, Nicola, Pajic, Marina, Patch, Ann-Marie, Chang, David K., Kassahn, Karin S., Bailey, Peter, Johns, Amber L., Miller, David, Nones, Katia, Quek, Kelly, Quinn, Michael C. J., Robertson, Alan J., Fadlullah, Muhammad Z. H., Bruxner, Tim J. C., Christ, Angelika N., Harliwong, Ivon, Idrisoglu, Senel, Manning, Suzanne, Nourse, Craig, Nourbakhsh, Ehsan, Wani, Shivangi, Wilson, Peter J., Markham, Emma, Cloonan, Nicole, Anderson, Matthew J., Fink, Lynn J., Holmes, Oliver, Kazakoff, Stephen H., Leonard, Conrad, Newell, Felicity, Poudel, Barsha, Song, Sarah, Taylor, Darrin, Waddell, Nick, Wood, Scott, Xu, Qinying, Wu, Jianmin, Pinese, Mark, Cowley, Mark J., Lee, Hong C., Jones, Marc D., Nagrial, Adnan M., Humphris, Jeremy, Chantrill, Lorraine A., Chin, Venessa, Steinmann, Angela M., Mawson, Amanda, Humphrey, Emily S., Colvin, Emily K., Chou, Angela, Scarlett, Christopher J., Pinho, Andreia V., Giry-Laterriere, Marc, Rooman, Ilse, Samra, Jaswinder S., Kench, James G., Pettitt, Jessica A., Merrett, Neil D., Toon, Christopher, Epari, Krishna, Nguyen, Nam Q., Barbour, Andrew, Zeps, Nikolajs, Jamieson, Nigel B., Graham, Janet S., Niclou, Simone P., Bjerkvig, Rolf, Grützmann, Robert, Aust, Daniela, Hruban, Ralph H., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Wolfgang, Christopher L., Morgan, Richard A., Lawlor, Rita T., Corbo, Vincenzo, Bassi, Claudio, Falconi, Massimo, Zamboni, Giuseppe, Tortora, Giampaolo, Tempero, Margaret A., Gill, Anthony J., Eshleman, James R., Pilarsky, Christian, Scarpa, Aldo, Musgrove, Elizabeth A., Pearson, John V., Biankin, Andrew V., Grimmond, Sean M., Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye H., Martyn-Smith, Mona, Thomas, Michelle T., Chin, Venessa T., Humphris, Jeremy L., Mead, Scott R., Pettit, Jessica, Tao, Jiang, DiPietro, Renee, Watson, Clare, Steinmann, Angela, Lee, Hong Ching, Wong, Rachel, Daly, Roger J., Sutherland, Robert L., Miller, David K., Gongora, Milena, Anderson, Matthew, Xu, Christina, Christ, Angelika, Bruxner, Tim, Quinn, Michael, Nagaraj, Shivashankar, Kazakoff, Stephen, Krisnan, Keerthana, Wood, David, Pavlakis, Nick, Guminski, Alex, Asghari, Ray, Pavey, Darren, Das, Amitabha, Cosman, Peter H., Ismail, Kasim, OʼConnnor, Chelsie, Lam Duncan McLeod, Vincent W., Pleass, Henry C., Richardson, Arthur, James, Virginia, Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Beilin, Maria, Feeney, Kynan, Nguyen, Nan Q., Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, OʼRourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Mountain, Angela, Schulick, Richard D., Hodgin, Mary, Beghelli, Stefania, Scardoni, Maria, Oien, Karen, and Hair, Jane

Published
2015
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21. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Author

Dreyer, Stephan B., primary, Upstill-Goddard, Rosie, additional, Paulus-Hock, Viola, additional, Paris, Clara, additional, Lampraki, Eirini-Maria, additional, Dray, Eloise, additional, Serrels, Bryan, additional, Caligiuri, Giuseppina, additional, Rebus, Selma, additional, Plenker, Dennis, additional, Galluzzo, Zachary, additional, Brunton, Holly, additional, Cunningham, Richard, additional, Tesson, Mathias, additional, Nourse, Craig, additional, Bailey, Ulla-Maja, additional, Jones, Marc, additional, Moran-Jones, Kim, additional, Wright, Derek W., additional, Duthie, Fraser, additional, Oien, Karin, additional, Evers, Lisa, additional, McKay, Colin J., additional, McGregor, Grant A., additional, Gulati, Aditi, additional, Brough, Rachel, additional, Bajrami, Ilirjana, additional, Pettitt, Stephan, additional, Dziubinski, Michele L., additional, Candido, Juliana, additional, Balkwill, Frances, additional, Barry, Simon T., additional, Grützmann, Robert, additional, Rahib, Lola, additional, Johns, Amber, additional, Pajic, Marina, additional, Froeling, Fieke E.M., additional, Beer, Phillip, additional, Musgrove, Elizabeth A., additional, Petersen, Gloria M., additional, Ashworth, Alan, additional, Frame, Margaret C., additional, Crawford, Howard C., additional, Simeone, Diane M., additional, Lord, Chris, additional, Mukhopadhyay, Debabrata, additional, Pilarsky, Christian, additional, Tuveson, David A., additional, Cooke, Susanna L., additional, Jamieson, Nigel B., additional, Morton, Jennifer P., additional, Sansom, Owen J., additional, Bailey, Peter J., additional, Biankin, Andrew V., additional, Chang, David K., additional, Allison, Sarah, additional, Beraldi, Dario, additional, Cameron, Euan, additional, Dreyer, Stephan, additional, Grimwood, Paul, additional, Kelly, Shane, additional, Marshall, John, additional, Martin, Sancha, additional, McDade, Brian, additional, McElroy, Daniel, additional, Ramsay, Donna, additional, Wright, Derek, additional, Jones, Marc D., additional, Hair, Jane, additional, Westwood, Paul, additional, Williams, Nicola, additional, Johns, Amber L., additional, Mawson, Amanda, additional, Scarlett, Christopher J., additional, Brancato, Mary-Anne L., additional, Rowe, Sarah J., additional, Simpson, Skye H., additional, Martyn-Smith, Mona, additional, Thomas, Michelle T., additional, Chantrill, Lorraine A., additional, Chin, Venessa T., additional, Chou, Angela, additional, Cowley, Mark J., additional, Humphris, Jeremy L., additional, Mead, R. Scott, additional, Nagrial, Adnan M., additional, Pettit, Jessica, additional, Pinese, Mark, additional, Rooman, Ilse, additional, Wu, Jianmin, additional, Tao, Jiang, additional, DiPietro, Renee, additional, Watson, Clare, additional, Steinmann, Angela, additional, Lee, Hong Ching, additional, Wong, Rachel, additional, Pinho, Andreia V., additional, Giry-Laterriere, Marc, additional, Daly, Roger J., additional, Sutherland, Robert L., additional, Grimmond, Sean M., additional, Waddell, Nicola, additional, Kassahn, Karin S., additional, Miller, David K., additional, Wilson, Peter J., additional, Patch, Ann-Marie, additional, Song, Sarah, additional, Harliwong, Ivon, additional, Idrisoglu, Senel, additional, Nourbakhsh, Ehsan, additional, Manning, Suzanne, additional, Wani, Shivangi, additional, Gongora, Milena, additional, Anderson, Matthew, additional, Holmes, Oliver, additional, Leonard, Conrad, additional, Taylor, Darrin, additional, Wood, Scott, additional, Xu, Christina, additional, Nones, Katia, additional, Fink, J. Lynn, additional, Christ, Angelika, additional, Bruxner, Tim, additional, Cloonan, Nicole, additional, Newell, Felicity, additional, Pearson, John V., additional, Bailey, Peter, additional, Quinn, Michael, additional, Nagaraj, Shivashankar, additional, Kazakoff, Stephen, additional, Waddell, Nick, additional, Krisnan, Keerthana, additional, Quek, Kelly, additional, Wood, David, additional, Samra, Jaswinder S., additional, Gill, Anthony J., additional, Pavlakis, Nick, additional, Guminski, Alex, additional, Toon, Christopher, additional, Asghari, Ray, additional, Merrett, Neil D., additional, Pavey, Darren, additional, Das, Amitabha, additional, Cosman, Peter H., additional, Ismail, Kasim, additional, O’Connnor, Chelsie, additional, Lam, Vincent W., additional, McLeod, Duncan, additional, Pleass, Henry C., additional, Richardson, Arthur, additional, James, Virginia, additional, Kench, James G., additional, Cooper, Caroline L., additional, Joseph, David, additional, Sandroussi, Charbel, additional, Crawford, Michael, additional, Gallagher, James, additional, Texler, Michael, additional, Forest, Cindy, additional, Laycock, Andrew, additional, Epari, Krishna P., additional, Ballal, Mo, additional, Fletcher, David R., additional, Mukhedkar, Sanjay, additional, Spry, Nigel A., additional, DeBoer, Bastiaan, additional, Chai, Ming, additional, Zeps, Nikolajs, additional, Beilin, Maria, additional, Feeney, Kynan, additional, Nguyen, Nan Q., additional, Ruszkiewicz, Andrew R., additional, Worthley, Chris, additional, Tan, Chuan P., additional, Debrencini, Tamara, additional, Chen, John, additional, Brooke-Smith, Mark E., additional, Papangelis, Virginia, additional, Tang, Henry, additional, Barbour, Andrew P., additional, Clouston, Andrew D., additional, Martin, Patrick, additional, O’Rourke, Thomas J., additional, Chiang, Amy, additional, Fawcett, Jonathan W., additional, Slater, Kellee, additional, Yeung, Shinn, additional, Hatzifotis, Michael, additional, Hodgkinson, Peter, additional, Christophi, Christopher, additional, Nikfarjam, Mehrdad, additional, Mountain, Angela, additional, Biobank, Victorian Cancer, additional, Eshleman, James R., additional, Hruban, Ralph H., additional, Maitra, Anirban, additional, Iacobuzio-Donahue, Christine A., additional, Schulick, Richard D., additional, Wolfgang, Christopher L., additional, Morgan, Richard A., additional, Hodgin, Mary, additional, Scarpa, Aldo, additional, Lawlor, Rita T., additional, Beghelli, Stefania, additional, Corbo, Vincenzo, additional, Scardoni, Maria, additional, Bassi, Claudio, additional, Tempero, Margaret A., additional, and Graham, Janet S., additional

Published
2021
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22. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Author

Biankin, Andrew V., Waddell, Nicola, Kassahn, Karin S., Gingras, Marie-Claude, Muthuswamy, Lakshmi B., Johns, Amber L., Miller, David K., Wilson, Peter J., Patch, Ann-Marie, Wu, Jianmin, Chang, David K., Cowley, Mark J., Gardiner, Brooke B., Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Pajic, Marina, Scarlett, Christopher J., Gill, Anthony J., Pinho, Andreia V., Rooman, Ilse, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Qinying, Nones, Katia, Lynn Fink, J., Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Kolle, Gabriel, Newell, Felicity, Pinese, Mark, Scott Mead, R., Humphris, Jeremy L., Kaplan, Warren, Jones, Marc D., Colvin, Emily K., Nagrial, Adnan M., Humphrey, Emily S., Chou, Angela, Chin, Venessa T., Chantrill, Lorraine A., Mawson, Amanda, Samra, Jaswinder S., Kench, James G., Lovell, Jessica A., Daly, Roger J., Merrett, Neil D., Toon, Christopher, Epari, Krishna, Nguyen, Nam Q., Barbour, Andrew, Zeps, Nikolajs, Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye L., Martyn-Smith, Mona, Thomas, Michelle T., Pettit, Jessica, Tao, Jiang, DiPietro, Renee, Watson, Clare, Wong, Rachel, Giry-Laterriere, Marc, Pavlakis, Nick, Guminski, Alex, Asghari, Ray, Pavey, Darren A., Das, Amitabha, Cosman, Peter H., Ismail, Kasim, O’Connor, Chelsie, Lam, Vincent W., McLeod, Duncan, Pleass, Henry C., Richardson, Arthur, James, Virginia, Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forrest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Beilin, Maria, Feeney, Kynan, Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, O’Rourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Mountain Victorian Cancer Biobank, Angela, Eshleman, James R., Schulick, Richard D., Wolfgang, Christopher L., Morgan, Richard A., Hodgin, Mary B., Lawlor, Rita T., Capelli, Paola, Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Pederzoli, Paolo, Tortora, Giampaolo, Bassi, Claudio, Kakkar, Nipun, Zhao, Fengmei, Qing Wu, Yuan, Wang, Min, Muzny, Donna M., Fisher, William E., Charles Brunicardi, F., Hodges, Sally E., Reid, Jeffrey G., Drummond, Jennifer, Chang, Kyle, Han, Yi, Lewis, Lora R., Dinh, Huyen, Buhay, Christian J., Beck, Timothy, Timms, Lee, Sam, Michelle, Begley, Kimberly, Brown, Andrew, Pai, Deepa, Panchal, Ami, Buchner, Nicholas, De Borja, Richard, Denroche, Robert E., Yung, Christina K., Serra, Stefano, Onetto, Nicole, Mukhopadhyay, Debabrata, Tsao, Ming-Sound, Shaw, Patricia A., Petersen, Gloria M., Gallinger, Steven, Hruban, Ralph H., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Tempero, Margaret A., Mann, Karen M., Jenkins, Nancy A., Perez-Mancera, Pedro A., Adams, David J., Largaespada, David A., Wessels, Lodewyk F. A., Rust, Alistair G., Stein, Lincoln D., Tuveson, David A., Copeland, Neal G., Musgrove, Elizabeth A., Scarpa, Aldo, Hudson, Thomas J., Sutherland, Robert L., Wheeler, David A., Pearson, John V., McPherson, John D., Gibbs, Richard A., and Grimmond, Sean M.

Published
2012
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23. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma

Author

Pérez-Mancera, Pedro A., Rust, Alistair G., van der Weyden, Louise, Kristiansen, Glen, Li, Allen, Sarver, Aaron L., Silverstein, Kevin A. T., Grützmann, Robert, Aust, Daniela, Rümmele, Petra, Knösel, Thomas, Herd, Colin, Stemple, Derek L., Kettleborough, Ross, Brosnan, Jacqueline A., Li, Ang, Morgan, Richard, Knight, Spencer, Yu, Jun, Stegeman, Shane, Collier, Lara S., ten Hoeve, Jelle J., de Ridder, Jeroen, Klein, Alison P., Goggins, Michael, Hruban, Ralph H., Chang, David K., Biankin, Andrew V., Grimmond, Sean M., Johns, Amber L., Mawson, Amanda, Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye L., Martyn-Smith, Mona, Chantrill, Lorraine A., Chin, Venessa T., Chou, Angela, Cowley, Mark J., Humphris, Jeremy L., Jones, Marc D., Mead, Scott R., Nagrial, Adnan M., Pajic, Marina, Pettit, Jessica, Pinese, Mark, Rooman, Ilse, Wu, Jianmin, Daly, Roger J., Musgrove, Elizabeth A., Sutherland, Robert L., Waddell, Nicola, Kassahn, Karin S., Miller, David K., Wilson, Peter J., Patch, Ann-Marie, Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Christina, Nones, Katia, Fink, Lynn J., Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Newell, Felicity, Pearson, John V., Samra, Jaswinder S., Gill, Anthony J., Pavlakis, Nick, Guminski, Alex, Toon, Christopher, Blankin, Andrew V., Asghari, Ray, Merrett, Neil D., Pavey, Darren A., Das, Amithabad, Cosman, Peter H., Ismail, Kasim, O’Connor, Chelsie, Lam, Vincent W., McLeod, Duncan, Pleass, Henry C., James, Virginia, Kench, James G., Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Texler, Michael, Forrest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Feeney, Kynan, Zeps, Nikolajs, Beilin, Maria, Nguyen, Nam Q., Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, O’Rourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Biobank, Victorian Cancer, Eshleman, James R., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Schulick, Richard D., Wolfgang, Christopher L., Morgan, Richard A., Lawlor, Rita T., Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Bassi, Claudio, Tempero, Margaret A., Wessels, Lodewyk F. A., Wood, Stephen A., Pilarsky, Christian, Largaespada, David A., Adams, David J., and Tuveson, David A.

Published
2012
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25. HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer

Author

Brunton, Holly, primary, Caligiuri, Giuseppina, additional, Cunningham, Richard, additional, Upstill-Goddard, Rosie, additional, Bailey, Ulla-Maja, additional, Garner, Ian M., additional, Nourse, Craig, additional, Dreyer, Stephan, additional, Jones, Marc, additional, Moran-Jones, Kim, additional, Wright, Derek W., additional, Paulus-Hock, Viola, additional, Nixon, Colin, additional, Thomson, Gemma, additional, Jamieson, Nigel B., additional, McGregor, Grant A., additional, Evers, Lisa, additional, McKay, Colin J., additional, Gulati, Aditi, additional, Brough, Rachel, additional, Bajrami, Ilirjana, additional, Pettitt, Stephen J., additional, Dziubinski, Michele L., additional, Barry, Simon T., additional, Grützmann, Robert, additional, Brown, Robert, additional, Curry, Edward, additional, Pajic, Marina, additional, Musgrove, Elizabeth A., additional, Petersen, Gloria M., additional, Shanks, Emma, additional, Ashworth, Alan, additional, Crawford, Howard C., additional, Simeone, Diane M., additional, Froeling, Fieke E.M., additional, Lord, Christopher J., additional, Mukhopadhyay, Debabrata, additional, Pilarsky, Christian, additional, Grimmond, Sean E., additional, Morton, Jennifer P., additional, Sansom, Owen J., additional, Chang, David K., additional, Bailey, Peter J., additional, Biankin, Andrew V., additional, Allison, Sarah, additional, Cooke, Susanna L., additional, Grimwood, Paul, additional, Kelly, Shane, additional, Marshall, John, additional, McDade, Brian, additional, McElroy, Daniel, additional, Ramsay, Donna, additional, Rebus, Selma, additional, Hair, Jane, additional, Westwood, Paul, additional, Williams, Nicola, additional, Duthie, Fraser, additional, Johns, Amber L., additional, Mawson, Amanda, additional, Scarlett, Christopher J., additional, Brancato, Mary-Anne L., additional, Rowe, Sarah J., additional, Simpson, Skye H., additional, Martyn-Smith, Mona, additional, Thomas, Michelle T., additional, Chantrill, Lorraine A., additional, Chin, Venessa T., additional, Chou, Angela, additional, Cowley, Mark J., additional, Humphris, Jeremy L., additional, Mead, R. Scott, additional, Nagrial, Adnan M., additional, Pettit, Jessica, additional, Pinese, Mark, additional, Rooman, Ilse, additional, Wu, Jianmin, additional, Tao, Jiang, additional, DiPietro, Renee, additional, Watson, Clare, additional, Steinmann, Angela, additional, Lee, Hong Ching, additional, Wong, Rachel, additional, Pinho, Andreia V., additional, Giry-Laterriere, Marc, additional, Daly, Roger J., additional, Sutherland, Robert L., additional, Grimmond, Sean M., additional, Waddell, Nicola, additional, Kassahn, Karin S., additional, Miller, David K., additional, Wilson, Peter J., additional, Patch, Ann-Marie, additional, Song, Sarah, additional, Harliwong, Ivon, additional, Idrisoglu, Senel, additional, Nourbakhsh, Ehsan, additional, Manning, Suzanne, additional, Wani, Shivangi, additional, Gongora, Milena, additional, Anderson, Matthew, additional, Holmes, Oliver, additional, Leonard, Conrad, additional, Taylor, Darrin, additional, Wood, Scott, additional, Xu, Christina, additional, Nones, Katia, additional, Fink, J. Lynn, additional, Christ, Angelika, additional, Bruxner, Tim, additional, Cloonan, Nicole, additional, Newell, Felicity, additional, Pearson, John V., additional, Quinn, Michael, additional, Nagaraj, Shivashankar, additional, Kazakoff, Stephen, additional, Waddell, Nick, additional, Krisnan, Keerthana, additional, Quek, Kelly, additional, Wood, David, additional, Samra, Jaswinder S., additional, Gill, Anthony J., additional, Pavlakis, Nick, additional, Guminski, Alex, additional, Toon, Christopher, additional, Asghari, Ray, additional, Merrett, Neil D., additional, Pavey, Darren, additional, Das, Amitabha, additional, Cosman, Peter H., additional, Ismail, Kasim, additional, O’Connnor, Chelsie, additional, Lam, Vincent W., additional, McLeod, Duncan, additional, Pleass, Henry C., additional, Richardson, Arthur, additional, James, Virginia, additional, Kench, James G., additional, Cooper, Caroline L., additional, Joseph, David, additional, Sandroussi, Charbel, additional, Crawford, Michael, additional, Gallagher, James, additional, Texler, Michael, additional, Forest, Cindy, additional, Laycock, Andrew, additional, Epari, Krishna P., additional, Ballal, Mo, additional, Fletcher, David R., additional, Mukhedkar, Sanjay, additional, Spry, Nigel A., additional, DeBoer, Bastiaan, additional, Chai, Ming, additional, Zeps, Nikolajs, additional, Beilin, Maria, additional, Feeney, Kynan, additional, Nguyen, Nan Q., additional, Ruszkiewicz, Andrew R., additional, Worthley, Chris, additional, Tan, Chuan P., additional, Debrencini, Tamara, additional, Chen, John, additional, Brooke-Smith, Mark E., additional, Papangelis, Virginia, additional, Tang, Henry, additional, Barbour, Andrew P., additional, Clouston, Andrew D., additional, Martin, Patrick, additional, O’Rourke, Thomas J., additional, Chiang, Amy, additional, Fawcett, Jonathan W., additional, Slater, Kellee, additional, Yeung, Shinn, additional, Hatzifotis, Michael, additional, Hodgkinson, Peter, additional, Christophi, Christopher, additional, Nikfarjam, Mehrdad, additional, Mountain, Angela, additional, Eshleman, James R., additional, Hruban, Ralph H., additional, Maitra, Anirban, additional, Iacobuzio-Donahue, Christine A., additional, Schulick, Richard D., additional, Wolfgang, Christopher L., additional, Morgan, Richard A., additional, Hodgin, Mary, additional, Scarpa, Aldo, additional, Lawlor, Rita T., additional, Beghelli, Stefania, additional, Corbo, Vincenzo, additional, Scardoni, Maria, additional, Bassi, Claudio, additional, Tempero, Margaret A., additional, and Graham, Janet S., additional

Published
2020
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28. Transcatheter microwave ablation can deliver deep and circumferential perivascular nerve injury without significant arterial injury to provide effective renal denervation

Author

Qian, Pierre C., primary, Barry, Michael A., additional, Lu, Juntang, additional, Al-Raisi, Sara, additional, Mina, Ashraf, additional, Ryan, Joshua, additional, Bandodkar, Sushil, additional, Alvarez, Shirley, additional, James, Virginia, additional, Ronquillo, John, additional, Varikatt, Winny, additional, Clayton, Zoe, additional, Chong, James, additional, Kovoor, Pramesh, additional, Pouliopoulos, Jim, additional, McEwan, Alistair, additional, Thiagalingam, Aravinda, additional, and Thomas, Stuart P., additional

Published
2019
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29. Museum Building by Students in Gifted Education.

Author

James, Virginia S.

Abstract

A review of research about museum education and a description of a group of gifted elementary school students' museum-building activities (display techniques, collection of resources, classification and arrangement methods, and work with outside donors) indicate that museum-building is a stimulating activity which encourages independent study and provides artistic and literary opportunities. (Author/CB)

Published
1987

30. TRANSCATHETER MICROWAVE ABLATION CAN PRODUCE DEEP CIRCUMFERENTIAL PERIVASCULAR ABLATION AND EFFECTIVE RENAL DENERVATION WITHOUT SIGNIFICANT ARTERIAL INJURY

Author

Qian, Pierre Cheng, primary, Barry, Michael, additional, Lu, Juntang, additional, Mina, Ashraf, additional, Ryan, Joshua, additional, Bandodkar, Sushil, additional, Alvarez, Shirley, additional, James, Virginia, additional, Ronquillo, John, additional, Varikatt, Winny, additional, Clayton, Zoe, additional, Chong, James, additional, Raisi, Sara Al, additional, Kovoor, Pramesh, additional, Pouliopoulos, Jim, additional, McEwan, Alistair, additional, Thiagalingam, Aravinda, additional, and Thomas, Stuart, additional

Published
2018
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31. Transcatheter non-contact microwave ablation may enable circumferential renal artery denervation while sparing the vessel intima and media

Author

Qian, Pierre, primary, Barry, Michael, additional, Al-Raisi, Sara, additional, Kovoor, Pramesh, additional, Pouliopoulos, Jim, additional, Nalliah, Chrishan, additional, Bhaskaran, Abhishek, additional, Chik, William, additional, Kurup, Rahul, additional, James, Virginia, additional, Varikatt, Winny, additional, McEwan, Alistair, additional, Thiagalingam, Aravinda, additional, and Thomas, Stuart, additional

Published
2017
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32. Relay of Herpes Simplex Virus between Langerhans Cells and Dermal Dendritic Cells in Human Skin

Author

Kim, Min, primary, Truong, Naomi R., additional, James, Virginia, additional, Bosnjak, Lidija, additional, Sandgren, Kerrie J., additional, Harman, Andrew N., additional, Nasr, Najla, additional, Bertram, Kirstie M., additional, Olbourne, Norman, additional, Sawleshwarkar, Shailandra, additional, McKinnon, Kaylene, additional, Cohen, Ralph C., additional, and Cunningham, Anthony L., additional

Published
2015
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33. Mass. village market yields fine art find

Author

James, Virginia Stowell

Subjects
Hobbies and crafts
Abstract

'Favorite Finds?' How do you mean 'favorite'? Is it most valuable in money terms or in sentiment? In beauty or useful function? A special memory? Technically or creatively unique? I [...]

Published
2013

34. Wine cork with more questions than answers

Author

James, Virginia Stowell

Subjects
Hobbies and crafts
Abstract

My 'Favorite Find' has less mystery about it, for it is a beautiful silver wine bottle cork that was clearly a 25th anniversary gift long ago. It is engraved '1875-1900.' [...]

Published
2013

35. Relay of Herpes Simplex Virus between Langerhans Cells and Dermal Dendritic Cells in Human Skin.

Author

James, Virginia, Bosnjak, Lidija, Kim, Min, Truong, Naomi R., Sandgren, Kerrie J., Harman, Andrew N., Nasr, Najla, Bertram, Kirstie M., Cunningham, Anthony L., Sawleshwarkar, Shailandra, Olbourne, Norman, McKinnon, Kaylene, and Cohen, Ralph C.

Subjects
*HERPES simplex virus, *LANGERHANS cells, *DENDRITIC cells, *SKIN diseases, *HIV infection risk factors, *IMMUNE response
Abstract

The mechanism by which immunity to Herpes Simplex Virus (HSV) is initiated is not completely defined. HSV initially infects mucosal epidermis prior to entering nerve endings. In mice, epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to encounter HSV, but it is CD103+ dermal DCs that carry viral antigen to lymph nodes for antigen presentation, suggesting DC cross-talk in skin. In this study, we compared topically HSV-1 infected human foreskin explants with biopsies of initial human genital herpes lesions to show LCs are initially infected then emigrate into the dermis. Here, LCs bearing markers of maturation and apoptosis formed large cell clusters with BDCA3+ dermal DCs (thought to be equivalent to murine CD103+ dermal DCs) and DC-SIGN+ DCs/macrophages. HSV-expressing LC fragments were observed inside the dermal DCs/macrophages and the BDCA3+ dermal DCs had up-regulated a damaged cell uptake receptor CLEC9A. No other infected epidermal cells interacted with dermal DCs. Correspondingly, LCs isolated from human skin and infected with HSV-1 in vitro also underwent apoptosis and were taken up by similarly isolated BDCA3+ dermal DCs and DC-SIGN+ cells. Thus, we conclude a viral antigen relay takes place where HSV infected LCs undergo apoptosis and are taken up by dermal DCs for subsequent antigen presentation. This provides a rationale for targeting these cells with mucosal or perhaps intradermal HSV immunization. [ABSTRACT FROM AUTHOR]

Published
2015
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37. Birth year postcard is a special gift

Author

James, Virginia

Subjects
Hobbies and crafts
Abstract

Dear Eric, When my husband turned 100 this last July, with a party on our porch in New Harbor (Maine), a very thoughtful gift from a friend was a great [...]

Published
2010

38. Museum building by students in gifted education.

Author

James, Virginia S.

Abstract

A summary of familiar practices in museum education is followed by review of important principles for gifted programs and sequential description of an experience in museum building by gifted students in an elementary program. Museum building within the gifted program is shown to be a stimulating and comprehensive activity which encourages independent study in the sciences, provides artistic and literary opportunities through the use of outside donors, and may also initiate career interests in unexpected fields. [ABSTRACT FROM PUBLISHER]

Published
1987
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39. Learning Resources for Children

Author

James, Virginia White and Parton, Daisy

Abstract

Environmental resources are useful to the child only when they contribute to meeting his needs in life situations. The good teacher sees to it that the school experiences make sense to the child.

Published
1955
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41. HNF4Aand GATA6Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer

Author

Brunton, Holly, Caligiuri, Giuseppina, Cunningham, Richard, Upstill-Goddard, Rosie, Bailey, Ulla-Maja, Garner, Ian M., Nourse, Craig, Dreyer, Stephan, Jones, Marc, Moran-Jones, Kim, Wright, Derek W., Paulus-Hock, Viola, Nixon, Colin, Thomson, Gemma, Jamieson, Nigel B., McGregor, Grant A., Evers, Lisa, McKay, Colin J., Gulati, Aditi, Brough, Rachel, Bajrami, Ilirjana, Pettitt, Stephen J., Dziubinski, Michele L., Barry, Simon T., Grützmann, Robert, Brown, Robert, Curry, Edward, Allison, Sarah, Biankin, Andrew V., Chang, David K., Cooke, Susanna L., Dreyer, Stephan, Grimwood, Paul, Kelly, Shane, Marshall, John, McDade, Brian, McElroy, Daniel, Ramsay, Donna, Upstill-Goddard, Rosie, Rebus, Selma, Hair, Jane, Jamieson, Nigel B., McKay, Colin J., Westwood, Paul, Williams, Nicola, Duthie, Fraser, Biankin, Andrew V., Johns, Amber L., Mawson, Amanda, Chang, David K., Scarlett, Christopher J., Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye H., Martyn-Smith, Mona, Thomas, Michelle T., Chantrill, Lorraine A., Chin, Venessa T., Chou, Angela, Cowley, Mark J., Humphris, Jeremy L., Mead, R. Scott, Nagrial, Adnan M., Pajic, Marina, Pettit, Jessica, Pinese, Mark, Rooman, Ilse, Wu, Jianmin, Tao, Jiang, DiPietro, Renee, Watson, Clare, Steinmann, Angela, Lee, Hong Ching, Wong, Rachel, Pinho, Andreia V., Giry-Laterriere, Marc, Daly, Roger J., Musgrove, Elizabeth A., Sutherland, Robert L., Grimmond, Sean M., Waddell, Nicola, Kassahn, Karin S., Miller, David K., Wilson, Peter J., Patch, Ann-Marie, Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Christina, Nones, Katia, Fink, J. Lynn, Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Newell, Felicity, Pearson, John V., Quinn, Michael, Nagaraj, Shivashankar, Kazakoff, Stephen, Waddell, Nick, Krisnan, Keerthana, Quek, Kelly, Wood, David, Samra, Jaswinder S., Gill, Anthony J., Pavlakis, Nick, Guminski, Alex, Toon, Christopher, Asghari, Ray, Merrett, Neil D., Pavey, Darren, Das, Amitabha, Cosman, Peter H., Ismail, Kasim, O’Connnor, Chelsie, Lam, Vincent W., McLeod, Duncan, Pleass, Henry C., Richardson, Arthur, James, Virginia, Kench, James G., Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Zeps, Nikolajs, Beilin, Maria, Feeney, Kynan, Nguyen, Nan Q., Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, O’Rourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Mountain, Angela, Eshleman, James R., Hruban, Ralph H., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Schulick, Richard D., Wolfgang, Christopher L., Morgan, Richard A., Hodgin, Mary, Scarpa, Aldo, Lawlor, Rita T., Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Bassi, Claudio, Tempero, Margaret A., Nourse, Craig, Jamieson, Nigel B., Graham, Janet S., Pajic, Marina, Musgrove, Elizabeth A., Petersen, Gloria M., Shanks, Emma, Ashworth, Alan, Crawford, Howard C., Simeone, Diane M., Froeling, Fieke E.M., Lord, Christopher J., Mukhopadhyay, Debabrata, Pilarsky, Christian, Grimmond, Sean E., Morton, Jennifer P., Sansom, Owen J., Chang, David K., Bailey, Peter J., and Biankin, Andrew V.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4Aand GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC.

Published
2020
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45. ALBANY CARRIAGE DRIVING.

Author

James, Virginia

Abstract

The article discusses the highlights of the annual Carriage Driving Carnival held on April 5-6, 2014 at the property acquired by land owners Carol Hammond and Jim Oversby, and mentions topics that include the Solstice Dressage Series event and the role of Albany Stock Feeds as event sponsor.

Published
2014

46. CHILD ACCOUNTING.

Author

James, Virginia

Subjects
PUBLIC schools, PUBLIC institutions, EDUCATION, BUSINESS
Abstract

The article focuses on the book "Child Accounting," by Arthur B. Moehlman. This book gives an excellent discussion of the development of the field of child accounting and its present offerings. It is based on work extending over a period of four years following the reorganization of the Detroit Public Schools in 1919.

Published
1925

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