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36 results on '"Underwood, Patrick"'

5. Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors

Author

Kazi, Aslamuzzaman, primary, Ranjan, Alok, additional, Kumar M.V., Vasantha, additional, Agianian, Bogos, additional, Garcia Chavez, Martin, additional, Vudatha, Vignesh, additional, Wang, Rui, additional, Vangipurapu, Rajanikanth, additional, Chen, Liwei, additional, Kennedy, Perry, additional, Subramanian, Karthikeyan, additional, Quirke, Jonathan C.K., additional, Beato, Francisca, additional, Underwood, Patrick W., additional, Fleming, Jason B., additional, Trevino, Jose, additional, Hergenrother, Paul J., additional, Gavathiotis, Evripidis, additional, and Sebti, Said M., additional

Published
2023
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6. Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer.

Author

Tushoski-Alemán, Gerik W., Herremans, Kelly M., Underwood, Patrick W., Akki, Ashwin, Riner, Andrea N., Trevino, Jose G., Han, Song, and Hughes, Steven J.

Subjects
CD8 antigen, CD3 antigen, PANCREATIC cancer, LYMPHOCYTES, ENZYME-linked immunosorbent assay
Abstract

Background: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. Methods: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. Results: Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. Conclusion: In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer.

Author

Underwood, Patrick W., Ruff, Samantha M., and Pawlik, Timothy M.

Subjects
*IRINOTECAN, *COLORECTAL cancer, *DNA mismatch repair, *METASTASIS, *EPIDERMAL growth factor receptors, *VASCULAR endothelial growth factors
Abstract

Metastatic colorectal cancer remains a deadly malignancy and is the third leading cause of cancer-related death. The mainstay of treatment for metastatic colorectal cancer is chemotherapy, but unfortunately, even with recent progress, overall survival is still poor. Colorectal cancer is a heterogeneous disease, and the underlying genetic differences among tumors can define the behavior and prognosis of the disease. Given the limitations of cytotoxic chemotherapy, research has focused on developing targeted therapy based on molecular subtyping. Since the early 2000s, multiple targeted therapies have demonstrated efficacy in treating metastatic colorectal cancer and have received FDA approval. The epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and DNA mismatch repair pathways have demonstrated promising results for targeted therapies. As new gene mutations and proteins involved in the oncogenesis of metastatic colorectal cancer are identified, new targets will continue to emerge. We herein provide a summary of the updated literature regarding targeted therapies for patients with mCRC. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

Author

Biel, Thomas G., primary, Petrovskaya, Svetlana, additional, Mascia, Francesca, additional, Ju, Tongzhong, additional, Fashoyin-Aje, Lola, additional, Herremans, Kelly M., additional, Riner, Andrea N., additional, Underwood, Patrick W., additional, Gerber, Michael H., additional, Donoghue, Martha, additional, Trevino, Jose G., additional, and Rao, V. Ashutosh, additional

Published
2023
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10. Additional file 4 of Surgical resident experience with common bile duct exploration and assessment of performance and autonomy with formative feedback

Author

Nyren, Molly Q., Filiberto, Amanda C., Underwood, Patrick W., Abbott, Kenneth L., Balch, Jeremy A., Mas, Francesca Dal, Cobianchi, Lorenzo, Efron, Philip A., George, Brian C., Shickel, Benjamin, Upchurch, Gilbert R., Sarosi, George A., and Loftus, Tyler J.

Abstract

Additional file 4: Table S3. Table illustrating subgroup analysis data for laparoscopic common bile duct exploration case characteristics stratified by resident experience

Published
2023
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11. Additional file 6 of Surgical resident experience with common bile duct exploration and assessment of performance and autonomy with formative feedback

Author

Nyren, Molly Q., Filiberto, Amanda C., Underwood, Patrick W., Abbott, Kenneth L., Balch, Jeremy A., Mas, Francesca Dal, Cobianchi, Lorenzo, Efron, Philip A., George, Brian C., Shickel, Benjamin, Upchurch, Gilbert R., Sarosi, George A., and Loftus, Tyler J.

Abstract

Additional file 6: Table S4. Table illustrating subgroup analysis data for resident operative performance and autonomy during laparoscopic common bile duct exploration stratified by resident experience

Published
2023
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12. Additional file 3 of Surgical resident experience with common bile duct exploration and assessment of performance and autonomy with formative feedback

Author

Nyren, Molly Q., Filiberto, Amanda C., Underwood, Patrick W., Abbott, Kenneth L., Balch, Jeremy A., Mas, Francesca Dal, Cobianchi, Lorenzo, Efron, Philip A., George, Brian C., Shickel, Benjamin, Upchurch, Gilbert R., Sarosi, George A., and Loftus, Tyler J.

Abstract

Additional file 3: Fig. S1. Visual flowchart illustrating breakdown of cases, with 189 total cases performed with residents, 146 of which were laparoscopic and 43 were open. Of the 146 laparoscopic cases, 46 residents had one or more prior evaluations and 100 had no prior evaluations. Of the 43 open cases, 2 residents had one or more prior evaluations and 41 had no prior evaluations

Published
2023
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13. Additional file 1 of Surgical resident experience with common bile duct exploration and assessment of performance and autonomy with formative feedback

Author

Nyren, Molly Q., Filiberto, Amanda C., Underwood, Patrick W., Abbott, Kenneth L., Balch, Jeremy A., Mas, Francesca Dal, Cobianchi, Lorenzo, Efron, Philip A., George, Brian C., Shickel, Benjamin, Upchurch, Gilbert R., Sarosi, George A., and Loftus, Tyler J.

Abstract

Additional file 1: Table S1. Table which illustrates the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines

Published
2023
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14. Additional file 2 of Surgical resident experience with common bile duct exploration and assessment of performance and autonomy with formative feedback

Author

Nyren, Molly Q., Filiberto, Amanda C., Underwood, Patrick W., Abbott, Kenneth L., Balch, Jeremy A., Mas, Francesca Dal, Cobianchi, Lorenzo, Efron, Philip A., George, Brian C., Shickel, Benjamin, Upchurch, Gilbert R., Sarosi, George A., and Loftus, Tyler J.

Abstract

Additional file 2: Table S2. Table which illustrates examples of positive and negative language in dictations

Published
2023
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15. Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer

Author

Principe, Daniel R., primary, Aissa, Alexandre F., additional, Kumar, Sandeep, additional, Pham, Thao N. D., additional, Underwood, Patrick W., additional, Nair, Rakesh, additional, Ke, Rong, additional, Rana, Basabi, additional, Trevino, Jose G., additional, Munshi, Hidayatullah G., additional, Benevolenskaya, Elizaveta V., additional, and Rana, Ajay, additional

Published
2022
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17. XP-524 is a dual-BET/EP300 inhibitor that represses oncogenic KRAS and potentiates immune checkpoint inhibition in pancreatic cancer

Author

Principe, Daniel R., primary, Xiong, Rui, additional, Li, Yangfeng, additional, Pham, Thao N. D., additional, Kamath, Suneel D., additional, Dubrovskyi, Oleksii, additional, Ratia, Kiira, additional, Huang, Fei, additional, Zhao, Jiong, additional, Shen, Zhengnan, additional, Thummuri, Dinesh, additional, Daohong, Zhou, additional, Underwood, Patrick W., additional, Trevino, Jose, additional, Munshi, Hidayatullah G., additional, Thatcher, Gregory R. J., additional, and Rana, Ajay, additional

Published
2022
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19. Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-XL–Specific Degrader DT2216

Author

Thummuri, Dinesh, primary, Khan, Sajid, additional, Underwood, Patrick W., additional, Zhang, Peiyi, additional, Wiegand, Janet, additional, Zhang, Xuan, additional, Budamagunta, Vivekananda, additional, Sobh, Amin, additional, Tagmount, Abderrahmane, additional, Loguinov, Alexander, additional, Riner, Andrea N., additional, Akki, Ashwin S., additional, Williamson, Elizabeth, additional, Hromas, Robert, additional, Vulpe, Christopher D., additional, Zheng, Guangrong, additional, Trevino, Jose G., additional, and Zhou, Daohong, additional

Published
2021
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21. Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer

Author

Kazi, Aslamuzzaman, primary, Chen, Liwei, additional, Xiang, Shengyan, additional, Vangipurapu, Rajanikanth, additional, Yang, Hua, additional, Beato, Francisca, additional, Fang, Bin, additional, Williams, Terence M., additional, Husain, Kazim, additional, Underwood, Patrick, additional, Fleming, Jason B., additional, Malafa, Mokenge, additional, Welsh, Eric A., additional, Koomen, John, additional, Trevino, José, additional, and Sebti, Saïd M., additional

Published
2021
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23. Abstract 955: Long-term gemcitabine treatment reshapes the pancreatic tumor microenvironment and sensitizes murine carcinoma to combination immunotherapy

Author

Principe, Daniel R., primary, Narbutis, Matthew, additional, Kumar, Sandeep, additional, Park, Alex, additional, Viswakarma, Navin, additional, Dorman, Matthew J., additional, Kamath, Suneel D., additional, Grippo, Paul, additional, Fishel, Melissa L., additional, Hwang, Rosa F., additional, Thummuri, Dinesh, additional, Underwood, Patrick W., additional, Munshi, Hidayatullah G., additional, Trevino, Jose G., additional, and Rana, Ajay, additional

Published
2020
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24. Abstract 1172: Disparities in pancreatic ductal adenocarcinoma - the significance of Hispanic ethnicity, by subgroup analysis, and treatment facility on clinical outcomes

Author

Riner, Andrea N., primary, Underwood, Patrick W., additional, Yang, Kai, additional, Herremans, Kelly M., additional, Cameron, Miles E., additional, Chamala, Srikar, additional, Qiu, Peihua, additional, George, Thomas, additional, Permuth, Jennifer, additional, Merchant, Nipun B., additional, and Trevino, Jose G., additional

Published
2020
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25. Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy

Author

Principe, Daniel R., primary, Narbutis, Matthew, additional, Kumar, Sandeep, additional, Park, Alex, additional, Viswakarma, Navin, additional, Dorman, Matthew J., additional, Kamath, Suneel D., additional, Grippo, Paul J., additional, Fishel, Melissa L., additional, Hwang, Rosa F., additional, Thummuri, Dinesh, additional, Underwood, Patrick W., additional, Munshi, Hidayatullah G., additional, Trevino, Jose G., additional, and Rana, Ajay, additional

Published
2020
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27. MEF2c-Dependent Downregulation of Myocilin Mediates Cancer-Induced Muscle Wasting and Associates with Cachexia in Patients with Cancer

Author

Judge, Sarah M., primary, Deyhle, Michael R., additional, Neyroud, Daria, additional, Nosacka, Rachel L., additional, D'Lugos, Andrew C., additional, Cameron, Miles E., additional, Vohra, Ravneet S., additional, Smuder, Ashley J., additional, Roberts, Brandon M., additional, Callaway, Chandler S., additional, Underwood, Patrick W., additional, Chrzanowski, Stephen M., additional, Batra, Abhinandan, additional, Murphy, Meghan E., additional, Heaven, Jonathan D., additional, Walter, Glenn A., additional, Trevino, Jose G., additional, and Judge, Andrew R., additional

Published
2020
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28. Disparities in Pancreatic Ductal Adenocarcinoma—The Significance of Hispanic Ethnicity, Subgroup Analysis, and Treatment Facility on Clinical Outcomes

Author

Riner, Andrea N., primary, Underwood, Patrick W., additional, Yang, Kai, additional, Herremans, Kelly M., additional, Cameron, Miles E., additional, Chamala, Srikar, additional, Qiu, Peihua, additional, George, Thomas J., additional, Permuth, Jennifer B., additional, Merchant, Nipun B., additional, and Trevino, Jose G., additional

Published
2020
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29. Nicotine Induces IL-8 Secretion from Pancreatic Cancer Stroma and Worsens Cancer-Induced Cachexia

Author

Underwood, Patrick W., primary, Zhang, Dong Yu, additional, Cameron, Miles E., additional, Gerber, Michael H., additional, Delitto, Daniel, additional, Maduka, Michael U., additional, Cooper, Kyle J., additional, Han, Song, additional, Hughes, Steven J., additional, Judge, Sarah M., additional, Judge, Andrew R., additional, and Trevino, Jose G., additional

Published
2020
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30. Osteopenia is associated with wasting in pancreatic adenocarcinoma and predicts survival after surgery.

Author

Cameron, Miles E., Underwood, Patrick W., Williams, Iverson E., George, Thomas J., Judge, Sarah M., Yarrow, Joshua F., Trevino, Jose G., and Judge, Andrew R.

Subjects
*PANCREATIC surgery, *BONE density, *OSTEOPENIA, *MUSCLE mass, *WEIGHT loss, *PANCREATIC duct
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest of all common malignancies. Treatment is difficult and often complicated by the presence of cachexia. The clinical portrait of cachexia contributes to the poor prognosis experienced by PDAC patients and worsens therapeutic outcomes. We propose that low bone mineral density is a component of cachexia, which we explore herein through a retrospective review of all patients at our facility that underwent surgery for PDAC between 2011 and 2018 and compared to sex‐, age‐ and comorbidity‐matched control individuals. Data were abstracted from the medical record and pre‐operative computed tomography scans. Muscle mass and quality were measured at the L3 level and bone mineral density was measured as the radiation attenuation of the lumbar vertebral bodies. Patients with PDAC displayed typical signs of cachexia such as weight loss and radiologically appreciable deterioration of skeletal muscle. Critically, PDAC patients had significantly lower bone mineral density than controls, with 61.2% of PDAC patients categorized as osteopenic compared to 36.8% of controls. PDAC patients classified as osteopenic had significantly reduced survival (1.01 years) compared to patients without osteopenia (2.77 years). The presence of osteopenia was the strongest clinical predictor of 1‐ and 2‐year disease‐specific mortality, increasing the risk of death by 107% and 80%, respectively. Osteopenia serves as a test of 2‐year mortality with sensitivity of 76% and specificity of 58%. These data therefore identify impaired bone mineral density as a key component of cachexia and predictor of postoperative survival in patients with PDAC. The mechanisms that lead to bone wasting in tumor‐bearing hosts deserve further study. [ABSTRACT FROM AUTHOR]

Published
2022
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31. Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors

Author

Kazi, Aslamuzzaman, primary, Xiang, Shengyan, additional, Yang, Hua, additional, Chen, Liwei, additional, Kennedy, Perry, additional, Ayaz, Muhammad, additional, Fletcher, Steven, additional, Cummings, Christopher, additional, Lawrence, Harshani R., additional, Beato, Francisca, additional, Kang, Ya'an, additional, Kim, Michael P., additional, Delitto, Andrea, additional, Underwood, Patrick W., additional, Fleming, Jason B., additional, Trevino, Jose G., additional, Hamilton, Andrew D., additional, and Sebti, Said M., additional

Published
2019
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33. Local and Systemic Cytokine Profiling for Pancreatic Ductal Adenocarcinoma to Study Cancer Cachexia in an Era of Precision Medicine

Author

Gerber, Michael H., primary, Underwood, Patrick W., additional, Judge, Sarah M., additional, Delitto, Daniel, additional, Delitto, Andrea E., additional, Nosacka, Rachel L., additional, DiVita, Bayli B., additional, Thomas, Ryan M., additional, Permuth, Jennifer B., additional, Hughes, Steven J., additional, Wallet, Shannon M., additional, Judge, Andrew R., additional, and Trevino, Jose G., additional

Published
2018
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35. Grievances and the Genesis of Rebellion:Mutiny in the Royal Navy, 1740-1820

Author

Hechter, Michael Norman, Pfaff, Steven, Underwood, Patrick, Hechter, Michael Norman, Pfaff, Steven, and Underwood, Patrick

Abstract

Rebellious collective action is rare, but it can occur when subordinates are severely discontented and other circumstances are favorable. The possibility of rebellion is a check sometimes the only check on authoritarian rule. Although mutinies in which crews seized control of their vessels were rare events, they occurred throughout the Age of Sail. To explain the occurrence of this form of high-risk collective action, this article holds that shipboard grievances were the principal cause of mutiny. However, not all grievances are equal in this respect. We distinguish between structural grievances that flow from incumbency in a subordinate social position and incidental grievances that incumbents have no expectation of suffering. Based on a case-control analysis of incidents of mutiny compared with controls drawn from a unique database of Royal Navy voyages from 1740 to 1820, in addition to a wealth of qualitative evidence, we find that mutiny was most likely to occur when structural grievances were combined with incidental ones. This finding has implications for understanding the causes of rebellion and the attainment of legitimate social order more generally.

Published
2016

36. Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-X L -Specific Degrader DT2216.

Author

Thummuri D, Khan S, Underwood PW, Zhang P, Wiegand J, Zhang X, Budamagunta V, Sobh A, Tagmount A, Loguinov A, Riner AN, Akki AS, Williamson E, Hromas R, Vulpe CD, Zheng G, Trevino JG, and Zhou D

Subjects
Animals, Antineoplastic Agents pharmacology, Deoxycytidine pharmacology, Deoxycytidine therapeutic use, Humans, Mice, Mice, Inbred NOD, Pancreatic Neoplasms pathology, Piperazines pharmacology, Gemcitabine, Antineoplastic Agents therapeutic use, Deoxycytidine analogs & derivatives, Drug Resistance, Neoplasm drug effects, Pancreatic Neoplasms drug therapy, Piperazines therapeutic use, bcl-X Protein metabolism
Abstract

Pancreatic cancer is the third most common cause of cancer-related deaths in the United States. Although gemcitabine is the standard of care for most patients with pancreatic cancer, its efficacy is limited by the development of resistance. This resistance may be attributable to the evasion of apoptosis caused by the overexpression of BCL-2 family antiapoptotic proteins. In this study, we investigated the role of BCL-X L in gemcitabine resistance to identify a combination therapy to more effectively treat pancreatic cancer. We used CRISPR-Cas9 screening to identify the key genes involved in gemcitabine resistance in pancreatic cancer. Pancreatic cancer cell dependencies on different BCL-2 family proteins and the efficacy of the combination of gemcitabine and DT2216 (a BCL-X L proteolysis targeting chimera or PROTAC) were determined by MTS, Annexin-V/PI, colony formation, and 3D tumor spheroid assays. The therapeutic efficacy of the combination was investigated in several patient-derived xenograft (PDX) mouse models of pancreatic cancer. We identified BCL-X L as a key mediator of gemcitabine resistance. The combination of gemcitabine and DT2216 synergistically induced cell death in multiple pancreatic cancer cell lines in vitro In vivo , the combination significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice compared with the individual agents in pancreatic cancer PDX models. Their synergistic antitumor activity is attributable to DT2216-induced degradation of BCL-X L and concomitant suppression of MCL-1 by gemcitabine. Our results suggest that DT2216-mediated BCL-X L degradation augments the antitumor activity of gemcitabine and their combination could be more effective for pancreatic cancer treatment., (©2021 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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