- Email: [email protected]
LIPIODOL GIVEN INTRAARTERIALLY UNDER ANGIOTENSIN-II INDUCED HIGH BLOOD-PRESSURE
POSTERS of AST, ALT, AFP, total bilirubin, gamma globulin and GGT, and lowered serum albumin level were significantly associated with HCC in the univariate analysis. Age, AST, AFP, albumin and GGT remained significantly associated with HCC in the multivariate analysis, showing multivariate-adjusted OR (95% CI) of 4.83 (2.05– 11.35) for age (60+ vs. <60 years old), 5.12 (1.87–14.03) for AST (30+ vs. <30 IU/L), 7.80 (3.14–19.40) for AFP (6+ vs. <6 ng/mL), 3.40 (1.56–7.42) for albumin (≤4.3 vs. >4.3 g/dL) and 4.68 (1.61–13.60) for GGT (35+ vs. <35 IU/L). These five variables were combined into an easy-to-use summary score, which was found to have an increased sensitivity and specificity for the early diagnosis of HBV-associated HCC, Conclusions: Basic serum biochemical markers frequently included in routine health examination may be combined to derive a valid and cost-effective method for early diagnosis of HBV-associated HCC. A simple score system combining age, AST, AFP, albumin and GGT is proposed in this study. 986 MIR-129–2 SILENCING UPREGULATED SOX4 EXPRESSION IN CHRONIC HBV INFECTION-RELATED HCC M. Hao, Q. Xie, T. Zhang, Y. Wang, X. Chen, F. Lu. Department of Microbiology, Peking University Health Science Center, Beijing, China E-mail: [email protected] Background and Aims: Several recent reports indicated the aberrant expression of microRNA miR-129s in a variety of human tumors. SOX4 as a known target of miR-129s, has been shown to be over activated in some tumors. Here we demonstrated that epigenetic repression of miR-129–2 leads to SOX4 over expression in HBV infection related HCC. Methods: Taqman RT-PCR method and quantitative realtime RTPCR were used separately to assess the changes of miR-129–3p (mature form of miR-129–2) and its known target SOX4 gene expression in tumor and adjacent non-tumor liver tissues from HCC patients with evidences of chronic HBV infection, as well as liver cancer cell lines. U6 promoter driven miR-129–2 precursor over-expressing plasmid was used for cell proliferation assay in vitro using HepG2 cell line. The methylation status of miR-129–2 gene was quantificationally analyzed by a novel method based on DNA methylation-sensitive and methylation-depended restriction endonuclease digestion and consequent quantitative PCR. The significance of miR-129–2 methylation status, SOX4 expression and their associations with patients’ clinicopathological characteristics were statistically analyzed. Results: Compared to adjacent non-tumor tissues, miR-129–3p expression level in tumor was significantly low (p = 0.0005), while SOX4 was over expressed in tumor samples (p = 0.015). Furthermore, transient transfection and ectopic expression of miR129–2 precursor in HepG2 cell decreased endogenous cellular SOX4 expression in vitro. Quantificationally analysis of the methylation status of the CpG island in the promoter region of miR-129–2 gene in 75 cases showed hypermethylation in 43% (31/75) of HCC tumor tissues, and in only 16% (12/75) of matched nontumor tissues. Accordingly, we found that endogenous miR129–3p expression was down regulated in those tissues with miR129–2 gene hypermethylation. Same reversed correlations between increased promoter hypermethylation intensity and lower matured miR-129–3p expression, as well as the decreased miR-129–3p and up regulated SOX4 expression were also demonstrated in 5 HCC cell lines. Also, miR-129–2 gene promoter hypermethylation was found associated with tumor intrahepatic metastasis. Conclusions: Our data here indicate that miR-129–3p expression silencing caused by miR-129–2 promoter hypermethylation and consequent SOX4 over expression was associated to chronic HBV infection-related HCC. The work was supported by China National S&T Major Project (2009ZX10004-903).
987 TREATMENTS OF HEPATOMA AND OTHER ABDOMINAL CANCERS USING SMANCS/LIPIODOL GIVEN INTRAARTERIALLY UNDER ANGIOTENSIN-II INDUCED HIGH BLOOD-PRESSURE H. Maeda1 , A. Nagamitsu2 , K. Greish3 . 1 Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, 2 Nagamitsu Clinic, Fukuoka, Japan; 3 Department of Pharmaceutics, University of Utah, Salt Lake City, UT, USA E-mail: [email protected] Background and Aims: SMANCS is styrene-maleic acid copolymer (SMA) conjugated anticancer protein neocarzinostatin (NCS), which exhibit potent cytotoxic effect at nM level inhibiting DNA. It is an approved drug in Japan for hepatoma, and administered via the Seldinger method under X-ray guidance. Its efficient therapeutic effect with little adverse effect has been established. Methods: We have develop a method for highly enhanced tumorselective delivery of SMANCS by applying hypertensive condition induced by slow infusion of angiotensin (AT)-II at 10–50 ng /min in patients. The targeted blood pressure is 150–170 mmHg and maintained for 15–20 min during drug infusion via the proper hepatic artery in typical HCC cases. The hypertension returned to normal when AT infusion stopped within a few min. The drug concentration for HCC was 1.0 mg/ml, for metastatic liver cancer, for cancer of the gallbladder or bile duct was 1.2–1.3 mg/ml, renal cell cancer was 1.3–1.5 mg/ml. The volume of the drug is variable depend on the tumor size ranging from 1 ml to 4 ml. For massive tumor >5 cm) multiple infusions with a few weeks interval are recommended. Results: Since the drug (SMANCS/Lipiodol) remains selectively in tumor for prolonged time (>3 months) remarkable therapeutic effect are achieved with least side effect. Size reduction to less than (f) 50% can be achieved after 1–2 injections in 3–4 month mostly in almost all cases if the tip of catheter was properly located. The adverse effect due to AT induced hypertension is rare headache. The method can be applicable for not only HCC, but also for many difficult-to-treat advanced cancers as described above. The frequency of drug infusion is once in 2–4 months at first, subsequently less frequent. One of the major precautions is the overflow of the drug into the gastro duodenal artery, which may induce gastric/duodenal ulcer. Reference(s) [1] A. Nagamitsu et al, Jpn. J. Clin. Oncol. (2000) 39, 756–766. [2] H. Maeda et al, Eur. J. Pharm. Biopharm. (2009) 71, 409–419. [3] Maeda et al, J. Control. Release (2001) 74, 47–61. [4] L. Seymour et al, Int. J. Oncol. (1998) 12, 1217–1223.
988 EVALUATION OF LOCAL RECURRENCE AFTER TREATMENT FOR HEPATOCELLULAR CARCINOMA BY CONTRAST-ENHANCED ULTRASONOGRAPHY: COMPARISON WITH DYNAMIC COMPUTED TOMOGRAPHY AND/OR MAGNETIC RESONANCE IMAGING A. Martin-Algibez1 , I. Fernandez-Vazquez1 , C. Lopez-Martinez2 , 1 M.S. Gallego-Gallego2 , R. San Roman2 , C. Munoz-Codocero ˜ , G. Castellano-Tortajada1 . 1 Servicio Medicina Aparato Digestivo, 2 Servicio de Radiologia, H. 12 de Octubre, Madrid, Spain E-mail: [email protected] The assessment of the therapeutic response of a focal hepatocellular carcinoma (HCC) is usually performed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI), both expensive and with potential adverse effects. On the other hand, contrast-enhanced ultrasonography (CEUS) has shown to be an effective tool in the initial diagnostic of this tumour. Aim: To evaluate prospectively the effectiveness of CEUS for the diagnosis of the local recurrence after treatment for HCC in comparison with CT and/or MRI.
Journal of Hepatology 2011 vol. 54 | S363–S534
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987 TREATMENTS OF HEPATOMA AND OTHER ABDOMINAL CANCERS USING SMANCS/LIPIODOL GIVEN INTRAARTERIALLY UNDER ANGIOTENSIN-II INDUCED HIGH BLOOD-PRESSURE H. Maeda1 , A. Nagamitsu2 , K. Greish3 . 1 Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, 2 Nagamitsu Clinic, Fukuoka, Japan; 3 Department of Pharmaceutics, University of Utah, Salt Lake City, UT, USA E-mail: [email protected] Background and Aims: SMANCS is styrene-maleic acid copolymer (SMA) conjugated anticancer protein neocarzinostatin (NCS), which exhibit potent cytotoxic effect at nM level inhibiting DNA. It is an approved drug in Japan for hepatoma, and administered via the Seldinger method under X-ray guidance. Its efficient therapeutic effect with little adverse effect has been established. Methods: We have develop a method for highly enhanced tumorselective delivery of SMANCS by applying hypertensive condition induced by slow infusion of angiotensin (AT)-II at 10–50 ng /min in patients. The targeted blood pressure is 150–170 mmHg and maintained for 15–20 min during drug infusion via the proper hepatic artery in typical HCC cases. The hypertension returned to normal when AT infusion stopped within a few min. The drug concentration for HCC was 1.0 mg/ml, for metastatic liver cancer, for cancer of the gallbladder or bile duct was 1.2–1.3 mg/ml, renal cell cancer was 1.3–1.5 mg/ml. The volume of the drug is variable depend on the tumor size ranging from 1 ml to 4 ml. For massive tumor >5 cm) multiple infusions with a few weeks interval are recommended. Results: Since the drug (SMANCS/Lipiodol) remains selectively in tumor for prolonged time (>3 months) remarkable therapeutic effect are achieved with least side effect. Size reduction to less than (f) 50% can be achieved after 1–2 injections in 3–4 month mostly in almost all cases if the tip of catheter was properly located. The adverse effect due to AT induced hypertension is rare headache. The method can be applicable for not only HCC, but also for many difficult-to-treat advanced cancers as described above. The frequency of drug infusion is once in 2–4 months at first, subsequently less frequent. One of the major precautions is the overflow of the drug into the gastro duodenal artery, which may induce gastric/duodenal ulcer. Reference(s) [1] A. Nagamitsu et al, Jpn. J. Clin. Oncol. (2000) 39, 756–766. [2] H. Maeda et al, Eur. J. Pharm. Biopharm. (2009) 71, 409–419. [3] Maeda et al, J. Control. Release (2001) 74, 47–61. [4] L. Seymour et al, Int. J. Oncol. (1998) 12, 1217–1223.
988 EVALUATION OF LOCAL RECURRENCE AFTER TREATMENT FOR HEPATOCELLULAR CARCINOMA BY CONTRAST-ENHANCED ULTRASONOGRAPHY: COMPARISON WITH DYNAMIC COMPUTED TOMOGRAPHY AND/OR MAGNETIC RESONANCE IMAGING A. Martin-Algibez1 , I. Fernandez-Vazquez1 , C. Lopez-Martinez2 , 1 M.S. Gallego-Gallego2 , R. San Roman2 , C. Munoz-Codocero ˜ , G. Castellano-Tortajada1 . 1 Servicio Medicina Aparato Digestivo, 2 Servicio de Radiologia, H. 12 de Octubre, Madrid, Spain E-mail: [email protected] The assessment of the therapeutic response of a focal hepatocellular carcinoma (HCC) is usually performed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI), both expensive and with potential adverse effects. On the other hand, contrast-enhanced ultrasonography (CEUS) has shown to be an effective tool in the initial diagnostic of this tumour. Aim: To evaluate prospectively the effectiveness of CEUS for the diagnosis of the local recurrence after treatment for HCC in comparison with CT and/or MRI.
Journal of Hepatology 2011 vol. 54 | S363–S534
S393