The pyruvate analog, 3-bromopyruvate, is an alkylating agent and a potent inhibitor of glycolysis. This antiglycolytic property of 3-bromopyruvate has recently been exploited to target cancer cells, as most tumors depend on glycolysis for their energy requirements. The anticancer effect of 3-bromopyruvate is achieved by depleting intracellular energy (ATP) resulting in tumor cell death. In this review, we will discuss the principal mechanism of action and primary targets of 3-bromopyruvate, and report the impressive antitumor effects of 3-bromopyruvate in multiple animal tumor models. We describe that the primary mechanism of 3-bromopyruvate is via preferential alkylation of GAPDH and that 3-bromopyruvate mediated cell death is linked to generation of free radicals. Research in our laboratory also revealed that 3-bromopyruvate induces endoplasmic reticulum stress, inhibits global protein synthesis further contributing to cancer cell death. Therefore, these and other studies reveal the tremendous potential of 3-bromopyruvate as an anticancer agent.
Purpose-To evaluate technical feasibility and experimental usefulness of percutaneous USguided implantation of Vx-2 carcinoma in rabbit liver.Materials and Methods-Forty-eight New Zealand White male rabbits were used. Solid tumor mass of Vx-2 carcinoma was harvested from carrier rabbit, and minced tumor cells were implanted. Twenty-four rabbits underwent percutaneous US-guided tumor implantation, and the same number of rabbits underwent open laparotomy tumor implantation. Tested parameters included technical success, procedural time, amount of anesthesia, recovery time, complications, tumor size, and regional tumor seeding.Results-A new percutaneous US-guided implantation was technically feasible in all rabbits. Evaluation parameters showed that the percutaneous US-guided implantation method is less invasive than the open laparotomy method. Targeting rate for left lateral lobe of implantation site was comparable in both methods (91.7% of percutaneous US-guided; 95.8% in open laparotomy). The success rate of tumor growth in the liver was 100% in both groups. However, in the group with USguidance, tumor seeding developed more frequently in five of 24 rabbits (20.8%) than in open laparotomy group (2/24, 8.3%). Five rabbits had thoracoabdominal wall needle tract seeding, and two rabbits had tumor seeding at both thoracoabdominal wall and intraperitoneal space.Conclusions-Percutaneous US-guided implantation of Vx-2 carcinoma in rabbit liver is a less invasive alternative to open laparotomy, achieving equally successful tumor growth in the liver. Although percutaneous US-guidance implantation method may not be considered for long-term survival study design because of the possibility of tumor seeding, it can be considered for nonsurvival study design.
Purpose The aim of this study was to characterize tumor growth of N1S1 cells implanted into the liver of Sprague Dawley rats in order to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH77777 cells. Materials and Methods N1S1 cells or McA-RH77777 cells were implanted into the liver of Sprague Dawley rats (n=20 and n=12, respectively) using ultrasound (US) and tumor growth was followed using US. Additionally, we compared the serum profile of 19 cytokines in naïve rats to tumor bearing rats. Results Both types of tumors were visible on US imaging 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm3 versus 82.3 mm3, respectively). Tumor volumes in both groups continued to increase reaching a mean tumor volume of 289 mm3 and 160 mm3 in the N1S1 and McA-RH7777 group, respectively, 2 weeks post tumor implant. By week 3, tumor volumes had declined considerably, and 6 (50%) tumors in the McA-RH7777 had spontaneously regressed, versus 2 (10%) tumors in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 group, respectively. In an N1S1 implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by up to 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an anti-tumor immune response. A similar trend was observed in a rat with a McA-RH77777 tumor, and the increase in cytokine levels was considerably more pronounced with an average increase of 320%. Conclusion We therefore conclude that this model cannot be used for survival studies, and should only be used with great caution in short-term studies that involve cancer therapies.
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