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Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model?

ABSTRACT: To characterize effects of combining radiofrequency (RF) ablation with proapoptotic intravenous liposome-encapsulated paclitaxel and doxorubicin on tumor destruction, apoptosis and heat-shock protein (HSP) production, intratumoral drug accumulation, and end-point survival.R3230 mammary adenocarcinomas (n = 177) were implanted in 174 rats in this animal care committee-approved study. Tumors received (a) no treatment, (b) RF ablation, (c) paclitaxel, (d) RF ablation followed by paclitaxel (RF ablation-paclitaxel), (e) paclitaxel before RF ablation (paclitaxel-RF ablation), (f) RF ablation followed by doxorubicin (RF ablation-doxorubicin), (g) paclitaxel followed by doxorubicin without RF ablation (paclitaxel-doxorubicin), or (h) paclitaxel before RF ablation, followed by doxorubicin (paclitaxel-RF ablation-doxorubicin). Tumor coagulation area and diameter were compared at 24-96 hours after treatment. Intratumoral paclitaxel uptake with and without RF ablation were compared. Immunohistochemical staining revealed cleaved caspase-3 and 70-kDa HSP (HSP70) expression. Tumors were randomized into eight treatment arms for Kaplan-Meier analysis of defined survival end-point (3.0-cm diameter).Paclitaxel-RF ablation increased tumor coagulation over RF ablation or paclitaxel (mean, 14.0 mm ± 0.9 [standard deviation], 6.7 mm ± 0.6, 2.5 mm ± 0.6, respectively; P < .001). Paclitaxel-RF ablation-doxorubicin had similar tumor coagulation (P < .05), compared with paclitaxel-RF ablation, at 24 and 96 hours. Mean intratumoral paclitaxel accumulation for paclitaxel-RF ablation (6.76 ?g/g ± 0.35) and RF ablation-paclitaxel (9.28 ?g/g ± 0.87) increased over that for paclitaxel (0.63 ?g/g ± 0.25, P < .001). Paclitaxel substantially increased apoptosis and decreased HSP70 expression at coagulation margin. Mean end-point survival for paclitaxel-RF ablation-doxorubicin (56.8 days ± 25.3) was greater, compared with that for paclitaxel-RF ablation or RF ablation-paclitaxel (17.6 days ± 2.5), RF ablation-doxorubicin (30.3 days ± 4.9, P < .002), or paclitaxel-doxorubicin (27.9 days ± 4.1, P < .001).Selecting adjuvant liposomal chemotherapies (paclitaxel, doxorubicin) to target cellular apoptosis and HSP production effectively increases RF ablation-induced tumor coagulation and end-point survival, and combined multidrug approach results in even better outcomes.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100500/-/DC1.

SUBMITTER: Yang W

PROVIDER: S-EPMC2984374 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model?

Yang Wei W Ahmed Muneeb M Elian Mostafa M Hady El-Shymma A el-SA Levchenko Tatyana S TS Sawant Rupa R RR Signoretti Sabina S Collins Michael M Torchilin Vladimir P VP Goldberg S Nahum SN

Radiology 20100921 3

<h4>Purpose</h4>To characterize effects of combining radiofrequency (RF) ablation with proapoptotic intravenous liposome-encapsulated paclitaxel and doxorubicin on tumor destruction, apoptosis and heat-shock protein (HSP) production, intratumoral drug accumulation, and end-point survival.<h4>Materials and methods</h4>R3230 mammary adenocarcinomas (n = 177) were implanted in 174 rats in this animal care committee-approved study. Tumors received (a) no treatment, (b) RF ablation, (c) paclitaxel, ( ...[more]

PMID: 20858851

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Project description:Background: Radiofrequency ablation (RFA) is a curative modality for hepatocellular carcinoma (HCC) patients who are not suitable for resection. It remains controversial whether a surgical or percutaneous approach is more appropriate for HCC. Method: A search was performed on the PubMed, Web of Science, Embase, and Cochrane Library databases from the date of database inception until April 17, 2021. Studies reporting outcomes of comparisons between surgical RFA (SRFA) and percutaneous RFA (PRFA) were included in this study. The meta-analysis was performed using the Review Manager 5.3 and Stata 12.0 software. Result: A total of 10 retrospective studies containing 12 cohorts, involving 740 patients in the PRFA group and 512 patients in the SRFA group, were selected. Although the tumor size in PRFA group was smaller than the SRFA group (p = 0.007), there was no significant difference in complete ablation rate between the SRFA and PRFA groups (95.63% and 97.33%, respectively; Odds ratio [OR], 0.56; 95% confidence intervals [CI], 0.26-1.24; p = 0.15). However, the SRFA group showed a significantly lower local tumor recurrence than the PRFA group in the sensitivity analysis (28.7% in the PRFA group and 21.79% in the SRFA group, respectively; OR, 1.84; 95% CI, 1.14-2.95; p = 0.01). Pooled analysis data showed that the rate of severe perioperative complications did not differ significantly between the PRFA and SRFA groups (14.28% and 12.11%, respectively; OR, 1.30; 95% CI, 0.67-2.53; p = 0.44). There was no significant difference in the 1-, 3-, and 5-year overall survival rates, as well as the 1- and 3-year disease-free survival (DFS) between the PRFA and SRFA groups. The 5-year DFS of the PRFA group was significantly lower than the SRFA group (hazard ratio 0.73; 95% CI 0.54-0.99). Conclusion: Based on our meta-analysis, the surgical route was superior to PRFA in terms of local control rate. Furthermore, the surgical approach did not increase the risk of major complications.

Project description:Background/aimRecent studies have suggested that periportal location of percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered as one of the independent risk factors for local tumor progression (LTP). However, the long-term therapeutic outcomes of percutaneous RFA as the first-line therapy for single periportal HCCand corresponding impacts on tumor recurrence or progression are still unclear.Materials and methodsFrom February 2011 to October 2020, a total of 233 patients with single nodular HCC ≤ 5 cm who underwent RFA ± transarterial chemoembolization (TACE) as first-line therapy was enrolled and analyzed, including 56 patients in the periportal group and 177 patients in the nonperiportal group. The long-term therapeutic outcomes between the two groups were compared, risk factors of tumor recurrence or progression were evaluated.ResultsThe LTP rates at 1, 3, and 5 years were significantly higher in the periportal group than those in the nonperiportal group (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year overall survival (OS) rates in the periportal group were significantly worse than those in the nonperiportal group (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P<0.0001). In the subgroup of single HCC ≤ 3 cm, patients with periportal HCC showed significantly worse LTP P = 0.0006) and OS (P<0.0001) after RFA than patients with single nonperiportal HCC; The univariate and multivariate analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. Furthermore, patients with single periportal HCC had significantly higher risk for IDR(P = 0.0012), PVTT(P<0.0001) and extrahepatic recurrence(P = 0.0010) after RFA than those patients with single nonperiportal HCC. .ConclusionThe long-term therapeutic outcomes of RFA as the first-line therapy for single periportal HCC were worse than those for single nonperiportal HCC, an increased higher risk of tumor recurrence or progression after RFA was significantly associated with periportal HCC.

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Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model?

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Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model?

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