The questions raised on the thread about toxicity are important. However, it should be understood that the patent is a highly detailed description of many instances of the use of 3-BP at many dosage ranges and with varying purposes in regard to describing aspects of treatment. After reading the patent in its entirety one realizes how non-toxic 3-BP treatment is when used in the manner described at the indicated therapeutic dosages for the selected purposes.
It should be noted that in the below quote they are using 0.5 mM of 3-BP. In other parts of the patent they use 20, 25, and up to 50 mM 3-BP (that is the molarity used was up to 100 times higher). Yet, it needs to be clearly understood that the patent is describing various methods and dosages that are not directly comparable. For instance, the 2.5 ml of 20 mM 3-BP in example 24 was in the context of intravenous administration of the drug. Toxicity arose from this dosage scheme.
However, in example 17, 25 ml of .5 mM 3-BP injected intraarterially had a dramatic treatment effect with no detectable toxicity. It should be understood that directly targeting liver tumors in this way would presumably not expose other organs to the risk of toxicity arising from 3-BP treatment. In such a procedure there might be a method of actively diluting the 3-BP at the end of treatment, in order that no other organ would be exposed to concentrated 3-BP. Yet, once the blood supply was reopened rapid dilution would occur spontaneously once the 3-BP mixed with the blood. The so called TACE procedure (direct targeting of the liver) was used in the German report.
For Example,
"Example 17: Direct Intraarterial Injection of 3-BrPA into Liver Implanted VX2 Tumors Selectively Inhibits the Viability of Cells Therein without Altering the Viability of Surrounding Liver Tissue.
To test our hypothesis that direct intraarterial injection of a potent inhibitor of cell ATP production (3-BrPA) may selectively inhibit the viability of cells within the tumor, we employed the established VX2 tumor model for reasons described above. Small chunks of a donor VX2 tumor were minced, surgically implanted in the livers of 6 rabbits/experiment, and allowed to grow for 14 days (Figure 2A). At this time, the single well- delineated tumor that developed in each liver exhibited a high degree of arterial vascularization due to the onset of angiogenesis. After fasting the animals for 24 hours and administering anesthesia, a catheter was carefully inserted into the femoral artery and guided by fluoroscopy into the hepatic artery to a position near the tumor site (Figure 2B). Then, a single bolus injection of 3-BrPA was delivered in about 2 min directly into the artery. Animals treated identically, but not receiving 3-BrPA served as controls. Optimal results were obtained by delivering 25 ml 0.5 mM 3-BrPA, waiting 4 days, and then excising and subjecting each tumor, and the surrounding liver tissue, to histological analysis. The results obtained from this novel approach proved to be quite dramatic.
Compared to control "untreated" tumors, where representative sections (7 slides/tumor) obtained outside the central core region revealed nearly 100 % viable cells (Figure 2C), similarly located sections obtained from tumors treated with 3-BrPA (Figure 2D) contained almost all non- viable cells (nearly 100 % necrosis). Viable tumor cells were detected only in small areas near arteries feeding the tumors (Figure 2E), and at the tumor periphery where sinusoidal blood is available. This may reflect more active mitochondria in these oxygen rich environments that are not completely debilitated at the concentrations of 3- BrPA used. Significantly, no damage occurred to liver tissue surrounding tumors that had been treated with 3-BrPA (Figures 2F and 2G). These results, reproduced in a number of experiments, were subjected to statistical evaluation. Tumors untreated with 3-BrPA (controls) contain 74 ± 5% viable cells in the entire population (Figure 2H, 1st column). The remaining cells, located within the hypoxic tumor core, have already become non-viable, a common feature of rapidly growing solid tumors. Treatment with a single intraarterial injection of 3-BrPA decreases the number of viable cells to 16 ± 5% (Figure 2H, 2nd column), thus increasing the total number of nonviable cells in the population to 84 ± 5% (P< 0.05). The maximal number of non-viable cells observed in any one experiment was 90%. In sharp contrast, the surrounding liver tissue remained completely viable in all cases examined (Figure 2H, 3rd and 4th columns)."
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Read your own rat study, which you quoted here:
