Pancreatic cancer ascites xenograft-an expeditious model mirroring advanced therapeutic resistant disease
Bibliographic record
Abstract
// Talia Golan 1, 2, * , Chani Stossel 1, * , Michael Schvimer 3 , Dikla Atias 1 , Sharon Halperin 1 , Ella Buzhor 1 , Maria Raitses-Gurevich 1 , Keren Cohen 1 , Sara Pri-Chen 4 , Julie Wilson 5 , Robert E. Denroche 6 , Ilinca Lungu 6 , John M.S. Bartlett 5 , Faridah Mbabaali 5 , Yosef Yarden 7 , Nishanth Belugali Nataraj 7 , Steven Gallinger 5, 6 and Raanan Berger 2, 8 1 Pancreatic Cancer Translational Research Laboratory, Oncology Institute, Sheba Medical Center, Tel Hashomer, Israel 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 3 Pathology Department, Sheba Medical Center, Tel Hashomer, Israel 4 Microsurgery Laboratory, Eye Institute, Sheba Medical Center, Tel Hashomer, Israel 5 Ontario Institute for Cancer Research, Toronto, Canada 6 Department of Surgery, University Health Network, Toronto, Canada 7 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel 8 Oncology Institute, Sheba Medical Center, Tel Hashomer, Israel * These authors contributed equally to this work Correspondence to: Talia Golan, email: Talia.Golan@sheba.health.gov.il Keywords: pancreatic ductal adenocarcinoma (PDAC), metastatic, ascites, whole genome sequencing (WGS), patient derived xenograft (PDX) Received: September 26, 2016 Accepted: April 04, 2017 Published: April 19, 2017 ABSTRACT Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20–30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts. Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research. Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".