Interstitial fluid pressure (IFP) and metastasis in a panel of tumor models
Bibliographic record
Abstract
1036 Introduction: High tumor IFP has been linked to poor drug uptake in patients, and there is strong evidence that high IFP is associated with spread of disease in cervix cancer patients treated with radiotherapy. To date, studies of IFP have focused on genetically identical tumor models, often grown sub-cutaneously, although evidence suggests that orthotopic models may be more clinically relevant. In this study we compared IFP in an array of murine and xenograft models, spontaneously arising or grown both intramuscularly (i/m) and orthotopically. Methods: KHT-C murine fibrosarcoma, or CaSki, Me180 and SiHa human cervix carcinoma cells were injected i/m into the hind legs of C3H or SCID mice. In addition, i/m tumors were used as donors to establish orthotopic cervix tumors from the CaSki, Me180 or SiHa models. Polyoma middle-T (PyMT) transgenic mice generated spontaneous mammary tumors, which were transplanted orthotopically into the 4th mammary gland of wild-type or SCID mice. IFP was measured at multiple points in all tumors using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. Results: All models showed intertumor heterogeneity in IFP values; KHT-C i/m: 2-42 mmHg, CaSki: i/m 6-63, cervix -2-17 mmHg, Me180: i/m 17-38, cervix 5-9 mmHg, SiHa: i/m 20-56, cervix 2-26 mmHg, PyMT: spontaneous 2-20 and transplanted 2-22 mmHg. The PyMT mice develop multiple tumors and there was significant variation between tumors in the same mouse (5-20 mmHg). Similarly, there was variation in IFP between two tumors transplanted into the same recipient and there was no correlation between donor and recipient IFP in the cervix carcinoma models or the PyMT model. No significant correlation was apparent between IFP values and metastatic burden in any of the tumor models. Furthermore, exposure of KHT-C and CaSki tumor cells to simulated high pressure in vitro prior to i/v injection in vivo did not significantly enhance experimental metastases presentation. Conclusions: The data show consistent intertumor heterogeneity in IFP in all models, irrespective of site, although median IFP values varied for the different tumors and different sites of growth. In particular, orthotopic transplantation of the cervix carcinoma cell lines gave tumors with lower IFP values than for tumors grown i/m. In addition, there was a lack of correlation in IFP values between recipient and donor tumors, indicative of individual tumor development irrespective of previous molecular interactions. Consistent with this, IFP measurement of different tumors in the same mouse using the PyMT spontaneous tumor model showed a high degree of variation. Whether this reflects differences in vascular density and permeability in the tumors is under investigation. Despite a broad range of IFP values in an assortment of different tumors, no correlation was observed between IFP and metastatic dissemination.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".