Stoppage of blood flow in 3-methylcholanthrene-induced autochthonous primary tumor due to a novel combretastatin A-4 derivative, AC7700, and its antitumor effect.
Bibliographic record
Abstract
BACKGROUND: Using several transplanted tumors in rats and mice, we have recently shown that the acute extensive necrosis of tumor nodules is caused by the systemic administration of AC7700, a novel combretastatin A-4 derivative, and that the necrosis can be attributed to irreversible stoppage of tumor blood flow (TBF). In this study, the antivascular and antitumor effects of AC7700 were tested on primary autochthonous tumor. MATERIAL AND METHODS: Primary sarcomas were induced in Fischer F344 rats by a single s.c. inoculation of 3-methylcholanthrene (MC) (4 mg/0.5 ml/head). Changes in TBF due to AC7700 were measured by hydrogen clearance technique. Antitumor effects of AC7700 were evaluated by histology and tumor growth inhibition. RESULTS: The earliest primary tumor appeared 77 days after MC treatment and the last tumor appeared after 273 days (median, 140 days). Once tumors occurred, they continued to grow slowly and never regressed spontaneously. The mean doubling time of tumors (n = 34) during exponential growth was 12.6 +/- 9.0 days (mean +/- SD) (range, 5.4-55.9 days). Blood flow in these slow-growing autochthonous tumors decreased highly significantly from 25.2 +/- 15.5 to 4.4 +/- 3.2 ml/min/100 g (24 electrodes)(P < 0.001) within 30 min due to rapid i.v. injection (0.15 ml/min) of 10 mg/kg AC7700 and the decreased TBF did not recover during the experimental period of 6 h. On the other hand, TBF did not change significantly due to 0.9% NaCl solution (10 electrodes). In addition, TBF immediately began to decrease following slow infusion (0.005 ml/min) of 10 mg/kg AC7700 and decreased by approximately 80% (12 electrodes) at 20 min after the start of AC7700 infusion. To evaluate the antitumor effect of AC7700 on the primary tumors, 10 mg/kg AC7700 was injected i.v. to tumor-bearing rats. Although in the natural course, such tumors never stop growing, the tumor growth was strongly inhibited by AC700 (n = 5). In 2 cases, tumors never regrew for the observation period of 45 days. Biopsy and histological findings (n = 5) showed that tumors underwent extensive necrosis, as was observed previously for transplanted tumors following AC7700 administration. CONCLUSION: From the present experiment it was demonstrated not only in transplanted tumors but also in carcinogen-induced autochthonous primary tumors that acute and sustained stoppage of TBF led to strong antitumor effects. The novel anticancer compound AC7700 might become a very useful therapeutic strategy against refractory cancers.
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) | 0.000 | 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) | 0.000 | 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".