Search

Your search keyword '"Krishna P. Epari"' showing total 3 results
Start Over Author "Krishna P. Epari"
3 results on '"Krishna P. Epari"'

1. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Author

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

Subjects
0301 basic medicine, HRD, homologous recombination deficiency, DNA Repair, PDAC, pancreatic ductal adenocarcinoma, Cell Culture Techniques, DMSO, dimethyl sulfoxide, Transcriptome, 0302 clinical medicine, Molecular Targeted Therapy, SV, structural variation, Original Research, Cancer, PDCL, patient-derived cell line, Gastroenterology, Organoids, PC, pancreatic cancer, oncology, PARP inhibitor, RNAseq, RNA sequencing, 030211 gastroenterology & hepatology, DNA Damage Response, ICGC, International Cancer Genome Consortium, DNA Replication, DNA repair, DNA damage, RPPA, reverse-phase protein array, EC50, median effective concentration, MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, Adenocarcinoma, Biology, DDR, DNA damage response, TOM, topological overlap measure, 03 medical and health sciences, Pancreatic Cancer, Cell Line, Tumor, Pancreatic cancer, GO, Gene Ontology, medicine, Humans, PDX, patient-derived xenograft, Hepatology, DNA replication, Personalized Medicine, Replication Stress, medicine.disease, Xenograft Model Antitumor Assays, Pancreatic Neoplasms, body regions, 030104 developmental biology, siRNA, small interfering RNA, Cancer research, Full Report: Basic and Translational—Pancreas, HR, homologous recombination, Homologous recombination, Biomarkers, DNA Damage
Abstract

Background & Aims Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. Methods We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. Results Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. Conclusions Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy., Graphical abstract

Published
2021
Full Text
View/download PDF

2. HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer

Author

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

Subjects
0301 basic medicine, Biology, Adenocarcinoma, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, GATA6, GSK-3, Pancreatic cancer, Cell Line, Tumor, GATA6 Transcription Factor, medicine, Biomarkers, Tumor, Humans, GSK3B, chromatin landscapes, metabolic targeting, intronic and distal promoters, medicine.disease, Phenotype, HNF4A, Chromatin, 030104 developmental biology, Hepatocyte nuclear factor 4, Hepatocyte Nuclear Factor 4, PDAC subtypes, oncology, Cancer research, therapeutic tolerance, 030217 neurology & neurosurgery, Carcinoma, Pancreatic Ductal
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, HNF4A and 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

3. The outcome of patients on the cholecystectomy waiting list in Western Australia 1999-2005

Author

Krishna P, Epari, Aqif S, Mukhtar, David R, Fletcher, Inian, Samarasam, and James B, Semmens

Subjects
Male, Native Hawaiian or Other Pacific Islander, Time Factors, Waiting Lists, Elective Surgical Procedures, Acute Disease, Humans, Cholecystectomy, Female, Gallstones, Western Australia, Patient Readmission
Abstract

Surgeons are noticing increasing numbers of cholecystectomy waiting list patients presenting with complications of their gallstones. In this study, we analysed the outcome of these to ascertain natural history and outcome.Data for 5298 waiting list patients in Western Australia, from 1999 to 2006, were analysed. Negative binomial regression was used to analyse waiting times data with Waitlist Year, Urgency Category and Aboriginality, after adjusting for Gender, Location and Age at Cholecystectomy.The overall median waiting time for surgery was 40 days (interquartile range (IQR) = 15-103). The median waiting times for Urgent, Semi-Urgent, and Routine categories were 21 (IQR = 8-63), 44 (IQR = 20-97) and 50 (IQR = 17-131) days, respectively. While waiting for surgery, 240 (5%) patients had gallstone-related admissions. Eighty (33.3%) patients had previous gallstone-related admissions prior to their enrolment on the waiting list. Analysis of the crude odds ratio showed that the probability of readmission during wait for surgery was three times more, when the surgery was not performed within the recommended time. Aboriginal and Torres Strait Islanders wait 1.77 times longer than non aboriginals (P0.001) and waiting time decreased with more recent calendar years. (P= 0.001) Patients in the metropolitan hospitals waited twice as long compared with the regional hospitals (P0.001).Approximately 5% of patients on the waiting list for an elective cholecystectomy were readmitted to the hospital for gallstone-related problems. Proper categorization of patients and definitive surgical treatment of acute gallbladder disease at index presentation might decrease this readmission rate. More effort needs to be made to ensure equity of access for gallstone patients.

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results