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2,105 results on '"Hawkins, William A."'

4. The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.

Author

Hagi, Takaomi, Vangveravong, Suwanna, Takchi, Rony, Gong, Qingqing, Goedegebuure, S, Tiriac, Herve, Van Tine, Brian, Powell, Matthew, Hawkins, William, and Spitzer, Dirk

Subjects
Humans, Animals, Mice, Female, Antineoplastic Agents, Apoptosis, Ovarian Neoplasms, Inhibitor of Apoptosis Proteins, Caspases, Cell Line, Tumor
Abstract

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.

Published
2024

5. Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer

Author

Bulle, Ashenafi, Liu, Peng, Seehra, Kuljeet, Bansod, Sapana, Chen, Yali, Zahra, Kiran, Somani, Vikas, Khawar, Iftikhar Ali, Chen, Hung-Po, Dodhiawala, Paarth B., Li, Lin, Geng, Yutong, Mo, Chia-Kuei, Mahsl, Jay, Ding, Li, Govindan, Ramaswamy, Davies, Sherri, Mudd, Jacqueline, Hawkins, William G., Fields, Ryan C., DeNardo, David G., Knoerzer, Deborah, Held, Jason M., Grierson, Patrick M., Wang-Gillam, Andrea, Ruzinova, Marianna B., and Lim, Kian-Huat

Published
2024
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16. Cultivating Innovation Capacity of Undergraduates in a Technology Commercialization Academy in Midwest America

Author

Chlebowski, Arthur L., McWilliams, Joshua D., Hawkins, William C., and El Tawil, Stephanie

Abstract

The Technology Commercialization Academy (TCA) was launched to promote the identification, assessment, and exploitation of economically viable innovations by undergraduates and retain those graduates in the southwest Indiana region. Further, as part of the I-69 Innovation Corridor initiative, the TCA was part of increasing the regional Innovation Index score 20% by 2025. Through the seven years of implementation, the program has determined that there is a crucial tool set that is necessary for new graduates entering industry, including instilling that innovation is a balance; innovation is agile; innovation must fail, pivot, and focus quickly; and lastly the program must realize its capabilities, be diverse in thought, and recognize that the personnel are key. By instilling these practices in the participants, using available programmatic information and surveys, 100% of job seekers post-graduation were employed within six months, 9% began their own startup from the program, and 64% of these high impact graduates stayed in southwest Indiana. Overall, the TCA program structure has shifted to demand side iterative processes that create long-tail value for the region and made the participants attractive hires who are keenly aware of practices to move from opportunity to execution.

Published
2021

22. Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology

Author

Panni, Usman Y., Chen, Michael Y., Zhang, Felicia, Cullinan, Darren R., Li, Lijin, James, C. Alston, Zhang, Xiuli, Rogers, S., Alarcon, A., Baer, John M., Zhang, Daoxiang, Gao, Feng, Miller, Christopher A., Gong, Qingqing, Lim, Kian-Huat, DeNardo, David G., Goedegebuure, S. Peter, Gillanders, William E., and Hawkins, William G.

Published
2023
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30. Digital Bariatric Surgery

Author

Yeung, Kai Tai Derek, Winter Beatty, Jasmine, Purkayastha, Sanjay, Hawkins, William J., Section editor, and Agrawal, Sanjay, editor

Published
2023
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34. High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival

Author

Storrs, Erik P., Chati, Prathamesh, Usmani, Abul, Sloan, Ian, Krasnick, Bradley A., Babbra, Ramandeep, Harris, Peter K., Sachs, Chloe M., Qaium, Faridi, Chatterjee, Deyali, Wetzel, Chris, Goedegebuure, S. Peter, Hollander, Thomas, Anthony, Hephzibah, Ponce, Jennifer, Khaliq, Ateeq M., Badiyan, Shahed, Kim, Hyun, Denardo, David G., Lang, Gabriel D., Cosgrove, Natalie D., Kushnir, Vladimir M., Early, Dayna S., Masood, Ashiq, Lim, Kian-Huat, Hawkins, William G., Ding, Li, Fields, Ryan C., Das, Koushik K., and Chaudhuri, Aadel A.

Published
2023
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35. Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study

Author

Park, Lauren K., Lim, Kian-Huat, Volkman, Jonas, Abdiannia, Mina, Johnston, Hannah, Nigogosyan, Zack, Siegel, Marilyn J., McGill, Janet B., McKee, Alexis M., Salam, Maamoun, Zhang, Rong M., Ma, Da, Popuri, Karteek, Chow, Vincent Tze Yang, Beg, Mirza Faisal, Hawkins, William G., Peterson, Linda R., and Ippolito, Joseph E.

Published
2023
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37. Sassafras

Author

Hawkins, William, American writer

Subjects
Sassafras (Short story), Literature/writing
Abstract

She was at the kitchen table watching the microwave clock leave midnight. Ron had promised he'd be back by half past eleven. Before he left, he'd said, 'I'm too old [...]

Published
2024

38. Thin-shell concrete floors for sustainable buildings

Author

Hawkins, William John, Orr, John, Shepherd, Paul, and Ibell, Tim

Subjects
624.1, Concrete shells, Structural optimisation, Building structures, Floors, Embodied carbon, Construction, Sustainability, textile reinforced concrete
Abstract

Rapid urbanisation and population growth is driving unprecedented levels of building construction. Over the next 40 years, approximately 230 billion square meters of new floor area will be constructed globally, a doubling of existing building stock. Already, the production of concrete and steel accounts for a third of worldwide industrial CO2 emissions, representing a major opportunity, and responsibility, for structural engineers to contribute towards a low-carbon future through efficient design. A significant majority of the structural material in a typical building exists within the floors, making these a prime target for material reductions. This dissertation shows that thin shell concrete floors are a viable alternative to typical slabs and beams in multi-storey buildings. Switching the dominant structural behaviour from bending to membrane action increases efficiency, enabling significant embodied carbon reductions. A system is proposed featuring pre-cast textile reinforced concrete shells of uniform thickness and shallow depth, supported at columns, with a network of prestressed steel tension ties. A lightweight foamed concrete fill is cast above the shells to provide a level top surface and transfer floor loads to the shell. The structural behaviour of this system is explored through a series of computational and experimental investigations, leading to refinement of the design, exploration of construction methods and the development of a complete design methodology incorporating novel theoretical work. The shells feature optimised singly-curved groin vault geometry. This provides efficient structural performance whilst simultaneously minimising construction complexity. Thus, a practical and scalable solution is proposed, which is shown to offer considerable embodied carbon savings over typical concrete and steel floor structures. This work provides a robust platform for future refinement and large-scale implementation of thin-shell concrete floors for sustainable buildings.

Published
2020
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43. Pancreas Cancer‐Associated Weight Loss

Author

Hendifar, Andrew E, Petzel, Maria QB, Zimmers, Teresa A, Denlinger, Crystal S, Matrisian, Lynn M, Picozzi, Vincent J, Rahib, Lola, Hendifar, Andrew, Tuli, Richard, Wolpin, Brian, Hidalgo, Manuel, Ryan, David, Hingorani, Sunil, Chiorean, Elena Gabriela, Coveler, Andrew, O'Reilly, Eileen, Balachandran, Vinod, Simeone, Diane, Lowy, Andrew, Fanta, Paul, Kurzrock, Razelle, Reid, Tony, Ko, Andrew, Collisson, Eric, Tempero, Margaret, Kindler, Hedy, George, Thomas, Trevino, Jose, Vonderheide, Robert, Beatty, Gregory, Picozzi, Vincent, Mandelson, Margaret, Wang‐Gillam, Andrea, Hawkins, William, Fleshman, Julie, Maitra, Anirban, Manax, Victoria, and Matrisian, Lynn

Subjects
Pancreatic Cancer, Cancer, Clinical Research, Digestive Diseases, Rare Diseases, Prevention, Nutrition, Clinical Trials and Supportive Activities, Cachexia, Humans, Pancreatic Neoplasms, Prevalence, Quality of Life, Weight Loss, Pancreatic cancer, Weight loss, Anorexia, Malabsorption, Supportive care, Precision Promise Consortium, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Unintentional weight loss in patients with pancreatic cancer is highly prevalent and contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Weight loss in pancreatic cancer can be due to anorexia, malabsorption, and/or cachexia. Proper supportive care can stabilize or reverse weight loss in patients and improve outcomes. We review the literature on supportive care relevant to pancreatic cancer patients, and offer evidence-based recommendations that include expert nutritional assessment, counseling, supportive measures to ensure adequate caloric intake, pancreatic enzyme supplementation, nutritional supplement replacement, orexigenic agents, and exercise. Pancreatic Cancer Action Network-supported initiatives will spearhead the dissemination and adoption of these best supportive care practices. IMPLICATIONS FOR PRACTICE: Weight loss in pancreatic cancer patients is endemic, as 85% of pancreatic cancer patients meet the classic definition of cancer cachexia. Despite its significant prevalence and associated morbidity, there is no established approach to this disease entity. It is believed that this is due to an important knowledge gap in understanding the underlying biology and lack of optimal treatment approaches. This article reviews the literature regarding pancreas cancer-associated weight loss and establishes a new framework from which to view this complex clinical problem. An improved approach and understanding will help educate clinicians, improve clinical care, and provide more clarity for future clinical investigation.

Published
2019

44. A diagnosis reconsidered: the symptomatic gallbladder remnant

Author

Grossman, Julie G, Johnston, William R, Fowler, Kathryn J, Williams, Gregory A, Hammill, Chet W, and Hawkins, William G

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Clinical Research, Pain Research, Cholangiopancreatography, Endoscopic Retrograde, Cholangiopancreatography, Magnetic Resonance, Cholecystectomy, Gallbladder Diseases, Humans, Retrospective Studies, Partial cholecystectomy, Remnant gallbladder, Retained gallbladder
Abstract

BACKGROUND:Patients can present with symptomatic gallbladder disease after cholecystectomy due to a remnant gallbladder. This is a rare problem and challenging diagnosis with limited prior characterization; thus, we present a large series of patients with a gallbladder remnant. METHODS:A retrospective review was performed of all patients presenting with symptomatic gallbladder remnant at a tertiary care center from 2002 to 2016. Data on presenting symptoms, diagnostic tests, treatments, and follow-up were collected. RESULTS:Thirty-one patients diagnosed and treated for a symptomatic gallbladder remnant were identified. The most common presenting symptoms included right upper quadrant pain (87%) and nausea (55%). The median time from symptom presentation to definitive diagnosis was 60 days. Diagnostic modalities utilized in the evaluation of these patients demonstrated that endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography were effective with sensitivities of 85% and 90%, respectively. Twenty-three (76.2%) patients underwent completion cholecystectomy, which proved to be definitive treatment. Additionally, eight (25.8%) patients were non-operative candidates and underwent endoscopic retrograde cholangiopancreatography and sphincterotomy, three of whom developed recurrent symptoms. CONCLUSION:A symptomatic gallbladder remnant after cholecystectomy is infrequently seen; however, the diagnosis should be considered in patients with recurrent biliary symptoms after cholecystectomy. Completion cholecystectomy can be challenging but is highly effective for definitive treatment.

Published
2019

45. Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer

Author

Cui Zhou, Daniel, Jayasinghe, Reyka G., Chen, Siqi, Herndon, John M., Iglesia, Michael D., Navale, Pooja, Wendl, Michael C., Caravan, Wagma, Sato, Kazuhito, Storrs, Erik, Mo, Chia-Kuei, Liu, Jingxian, Southard-Smith, Austin N., Wu, Yige, Naser Al Deen, Nataly, Baer, John M., Fulton, Robert S., Wyczalkowski, Matthew A., Liu, Ruiyang, Fronick, Catrina C., Fulton, Lucinda A., Shinkle, Andrew, Thammavong, Lisa, Zhu, Houxiang, Sun, Hua, Wang, Liang-Bo, Li, Yize, Zuo, Chong, McMichael, Joshua F., Davies, Sherri R., Appelbaum, Elizabeth L., Robbins, Keenan J., Chasnoff, Sara E., Yang, Xiaolu, Reeb, Ashley N., Oh, Clara, Serasanambati, Mamatha, Lal, Preet, Varghese, Rajees, Mashl, Jay R., Ponce, Jennifer, Terekhanova, Nadezhda V., Yao, Lijun, Wang, Fang, Chen, Lijun, Schnaubelt, Michael, Lu, Rita Jui-Hsien, Schwarz, Julie K., Puram, Sidharth V., Kim, Albert H., Song, Sheng-Kwei, Shoghi, Kooresh I., Lau, Ken S., Ju, Tao, Chen, Ken, Chatterjee, Deyali, Hawkins, William G., Zhang, Hui, Achilefu, Samuel, Chheda, Milan G., Oh, Stephen T., Gillanders, William E., Chen, Feng, DeNardo, David G., Fields, Ryan C., and Ding, Li

Published
2022
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47. Oligometastatic Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Chemotherapy With Nonoperative Intent of the Primary for Locoregional Complete Responders

Author

Schiff, Joshua P., Chin, Re-I, Roy, Amit, Mahapatra, Lily, Stowe, Hayley B., Andruska, Neal, Huang, Yi, Mutch, Matthew, Fields, Ryan C., Hawkins, William G., Doyle, Maria, Chapman, Will, Tan, Benjamin, Henke, Lauren E., Badiyan, Shahed N., DeSelm, Carl, Samson, Pamela P., Pedersen, Katrina, and Kim, Hyun

Published
2022
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49. Esophageal and gastric malignancies after bariatric surgery: a retrospective global study

Author

Gallardo, Carlos Sosa, Agustin, Cataldo, Wright, Fernando, Fuente, Ignacio, Carbajo, Miguel, Cal, Patricio, Chisholm, Jacob, Kow, Lilian, Tan, Michael H.L., Gan, Philip, Gananadha, Sivakumar, Felsenreich, Daniel M., Prager, Gerhard, Matthys, Chris, Himpens, Jacques M., Focquet, Marc A.M.R.M., Ramos, Almino, Nato, Manoel Galvano, Vidal, Thiago, Andalib, Amin, Siblini, Aya, Ferri, Lorenzo, Abdarabo, Lina, Nevo, Yehonatan, Pescarus, Radu, Yang, Wah, Hamed, Hosam, Liagre, Arnaud, Bergeat, Damien, Marie, De Montrichard, Martini, Francesco, Regis, François, Genser, Laurent, Skalli, Mehdi, Nedelcu, Marius, Smejkal, Milan, Kassir, Radwan, Nicolas, Regenet, Stier, Christine, Nedelcut, Dan-Sebastian, Christodoulidis, Grigorios, Vennapusa, Amar, Kermansaravi, Mohammad, Raziel, Asnat, Sakran, Nasser, Oldani, Alberto, Boru, Cristian Eugeniu, Mécheri, Fouzia, Ciccarese, Francesca, Cesana, Giovanni Carlo, Musella, Mario, Uccelli, Matteo, Foletto, Mirto, Auricchio, Pasquale, Olmi, Stefano, Seki, Yosuke, Kasteleijn, Anne, Van 'T Hof, Gerhard, Apers, Jan A., Hart, Judith W.H., Van De Sande, Justin S.L., Takkenberg, Marijn, Feskens, Pierre B.G.M., Snoekx, Rob, Plat, Victor D., Sandvik, Jorunn, Kalinowski, Piotr, Nabais, Celso, Al-Bahrani, Ahmed Z., Al Zoubi, Mohammad, Bettonica, Carla, Osorio, Javier, Tejedor-Tejada, Javier, Sanz, Lourdes M., Cuadrado, Marta, Moorjani, Rajesh Gianchandani, Yannick, Fringeli, Suter, Michel, Borbély, Yves, Joerg, Zehetner, Barajas-Gamboa, Juan S., Kroh, Matthew, Kisiel, Aaron P., Kamocka, Anna, Immanuel, Arul, Sgromo, Bruno, Gopinath, Bussa, Khoo, David, Mukherjee, Samrat, Pournaras, Dimitrios, Underwood, Tim, Griffiths, Ewen A., Miller, Glenn V., Jaretzke, Helen, Dmitrewski, Jan, Wadley, Martin S., Al-Housni, Ragad, Gillies, Richard S., Singhal, Rishi, Preston, Shaun R., Robinson, Steven John, Hawkins, William J., Adamo, Marco, El Kalaawy, Mohamed, Gossage, James, Crawford, Christopher B., Jaruvongvanich, Veeravich, Parmar, Chetan, Zakeri, Roxanna, Abouelazayem, Mohamed, Shin, Thomas H., Aminian, Ali, Mahmoud, Tala, Abu Dayyeh, Barham K., Wee, Melissa Y., Fischer, Laura, Daams, Freek, and Mahawar, Kamal

Published
2022
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