A162 DEFINING INNATE IMMUNE CELL MECHANISMS UPON <i>HELICOBACTER PYLORI</i> MEDIATED TUMORIGENESIS
Bibliographic record
Abstract
Abstract Aims Hypothesis: H. pylori interacts with eosinophils to inhibit degranulation, alter eosinophil gene expression and promote gastric tumorigenesis Aim 1: Elucidate the mechanisms underlying the interactions between eosinophils and H. pylori. Aim 2: Determine the role of eosinophils during H. pylori mediated gastric tumorigenesis. Methods Histological and immunofluorescent staining. Hemotoxilin and eosin staining is important to analyze gastric gland structure and parietal cell loss. Immunofluorescent staining is used to detect and localize specific antigens present in cells and cell membranes. Gastric organoids: Gastric organoids are an important tool for modelling dissease. Gastric organoids generated from adult stem cells from gastric glands depend on growth factors that mimic tissue regeneration. Bone marrow derived eosinophils: Bone marrow progenitor cells isolated from murine femur and tibia are easily converted into maturer eosinophils with the addition of cytokine interleukin-5. Results Addition of mouse derived eosinophils to gastric organoids significantly increases number of organoids. To understand the relationship between eosinophils and gastric epithelial cell (GEC) growth, I designed a co-culture experiment that involved incubating mature eosinophils with gastric glands in an extracellular matrix. These findings revealed a significant increase in the number of gastric organoids per well when eosinophils were present compared to the gastric organoids without eosinophils. This observation supports the hypothesis that eosinophils may play a crucial role in promoting gastric tumorigenesis. Exposure of mouse derived eosinophils to H. pylori significantly increases gastric organoid proliferation. To explore the impact of stimulating eosinophils prior to incubation with GECs I incubated the eosinophils with H. pylori. As expected, there was a significant increase in the number of organoids per well with the addition of uninfected eosinophils. Interestingly, when H. pylori incubated eosinophils were added to the gastric glands, there was a significant increase in the number of gastric organoids per well compared to uninfected eosinophils. Conclusions My preliminary findings have indicated that eosinophils can promote gastric epithelial stem cell proliferation. These results led me to ask how treatment of eosinophils with H. pylori subsequently impacts gastric organoid growth and gastric stem cell proliferation. Interestingly, I found H. pylori treated eosinophils increase growth and gastric stem cell proliferation. These results support my hypothesis as increased proliferation is considered a hallmark of tumorigenesis. There little known about resident and inflammatory GI eosinophils and the role of eosinophils during tumorigenesis in unknown. A better understanding of the role eosinophils play can uncover novel mechanisms to be targeted for therapeutic intervention. Funding Agencies CIHR
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".