RESUMEN
OBJECTIVE: To explore the antitumor role of the attenuated Salmonella typhimurium ΔppGpp with inducible cytolysin A (ClyA) in advanced stage of glioma. MATERIALS AND METHODS: The C6 rat glioma cells were orthotopically implanted by surgery into the caudate nucleus of rat brains. The rats were then randomly divided into the treatment group (SL + ClyA) (n=12), negative control group (SL) (n=12), and control group (phosphate-buffered saline [PBS]) (n=12). In the treatment group, the attenuated S. typhimurium were transformed with the plasmid-encoded antitumor gene ClyA. The expression of ClyA was controlled by the TetR-regulated promoter in response to extracellular doxycycline. The plasmid also contained an imaging gene lux to allow illumination of the tumor infected by the bacteria. The rat glioma C6 cells were implanted into the caudate nucleus of all rats. The engineered S. typhimurium and respective controls were injected intravenously into the rats 21 days after initial tumor implantation. The pathological analysis of the glioma tumor was performed at 21 days and 28 days (7 days after doxycycline treatment) postimplantation. All rats underwent MRI (magnetic resonance imaging) and bioluminescence study at 21 days and 28 days postimplantation to detect tumor volume. The differences between the three groups in tumor volume and survival time were analyzed. RESULTS: Advanced stage glioma was detected at 21 days postimplantation. Bioluminescence showed that the engineered S. typhimurium accumulated in glioma tumors and disappeared in the normal reticuloendothelial tissues 3 days after intravenous injection. MRI showed that the tumor volume in the S. typhimurium with ClyA group were significantly reduced compared to the bacteria alone and no bacteria groups 7 days post-doxycycline treatment (P<0.05), while the necrotic tumor volume in the S. typhimurium with ClyA group and S. typhimurium alone group increased significantly compared to the control group (P<0.01). In addition, the survival time was significantly prolonged in the bacteria-treated group compared to the PBS-treated control group (P<0.01). CONCLUSION: The engineered S. typhimurium can significantly induce cancer cell apoptosis in the tumor center and inhibit cancer cell proliferation in the outer zone of advanced glioma tumor, leading to a prolonged survival time in rats. In addition, the engineered S. typhimurium that carried the antitumor and imaging genes controlled by the TetR-regulated promoter have high delivery efficiency with tolerable side effects in rats.
RESUMEN
OBJECTIVE: To discuss the role of 3D-computed tomography angiography (3D-CTA) technology in reducing injuries of large meningioma surgery. METHODS: 3D-CTA preoperative examinations were done in 473 patients with large meningioma (simulated group). The images were analyzed by 3D post-processing workstation. By observing the major intracranial blood vessels, venous sinus, and the compression and invasion pattern in the nerve region, assessing risk level of the surgery, simulating the surgical procedures, the surgical removal plan, surgical routes and tumor blood-supplying artery embolisation plan were performed. Two hundred and fifty seven large meningioma patients who didn't underwent 3D-CTA preoperative examination served as control group. The incidence of postoperative complications, intraoperative blood transfusion and the operation time were compared between these two groups. RESULTS: Compared with the control group, the Simpson's grade I and II resection rate was 80.3% (380/473), similar with that of the control (81.3%, 209/257). The incidence of postoperative complications in 3D-CTA simulated group was 37.0% which was significantly lower than that (48.2%) of the control (P<0.01). The intraoperative blood supply for simulated group and the control was (523.4±208.1) mL and (592.0±263.3) mL, respectively, with significant difference between two groups (P<0.01). And the operation time [(314.8±106.3)] min was significantly lower in simulated group than that in the control [(358.4±147.9) min] (P<0.01). CONCLUSION: Application of 3D-CTA imaging technology in risk level assessment before large-scaled meningioma resection could assist in the rational planning of tumor resectin, surgical routes, and is helpful in reducing injuries and complications and enhancing the prognosis of the patients.