Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma

The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor,O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma—LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 nude mice; the mice were then randomized into two groups. To one group, TNP-470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was clearly demonstrated by tumor weight (0.97±0.34 g compared to 2.04±0.34 g,P<0.001) and -Fetoprotein value (93±59 g/L compared to 769±282 g/L,P<0.001). There was also an anti-metastatic effect of TNP-470. Lung metastases developed in only 1 of 12 mice in the treated group, while they developed in 6 of mice of the control group. No severe side-effect of TNP-470 was found in this study. In vitro study revealed that the purified hepatoma cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43 g/ml). These results suggest that the angiogenesis inhibitor TNP-470 has both strong antitumor and anti-metastatic effects on a human hepatocellular carcinoma model in nude mice.Abbreviations TNP-470 O-(chloroacetyl-carbamoyl) Fumagillol - MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide This work was partly supported by the CHina Medical Board of New York, grant 93-583, and a Leading Speciality grant of Shanghai Health Bureau     

重视肝癌的病因和预防

原发性肝癌(以下简称肝癌)是我国常见的恶性肿瘤之一.据世界卫生组织统计,目前每年新患肝癌749 000人,死亡664000人,新患者中53.5％为中国人[1].在我国各种恶性肿瘤的死亡顺位中,肝癌仅次于肺癌居第二位.肝癌的治疗近年取得了长足进步,但总体而言,预后仍差.故重视肝癌的病因与预防,仍甚为重要.     

SELDI-TOF MS profiling of serum for detection of laryngeal squamous cell carcinoma and the progression to lymph node metastasis

Objectives Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. Our study was to assess the use of surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for early detection of laryngeal squamous cell carcinoma (LSCC), establish predictive model, and accurately distinguish LSCC patients with or without lymph node metastasis. Methods A cohort of 252 serum samples with LSCC (n = 142) and normal control (n = 110) were consented into this study. These serum samples were randomly divided into training set (including 89 LSCC patients at stages I–II and 65 normal controls, 30 LSCC patients with lymph node metastasis) and blind testing set (including 53 LSCC patients at stages III–IV and 45 normal controls). Serum protein profiles on weak cationic exchange (WCX2) were performed by SELDI-TOF MS and then analyzed by Biomarker Wizard software. The Decision Tree classification algorithm and blind validation were determined by Biomarker Pattern Software (BPS). Results A panel of 18 biomarkers ranging 2–30 kDa was selected based on their collective contribution to the optimal separation between stages I–II LSCC patients and healthy controls. Among them, one candidate protein peak with an m/z value of 4,176 Da was selected to establish predictive model by BPS with sensitivity of 86.52% and specificity of 84.62%. The ability to detect LSCC patients was evaluated using blinding test data in stages III and IV cancer patients. A sensitivity of 84.91% and specificity of 82.22% were validated in blind testing set. Meanwhile 14 potential biomarkers could differentiate LSCC patients with or without lymph node metastasis (P < 0.05). Conclusions The high sensitivity and specificity achieved by the serum protein biomarkers show great potential for the early detection of LSCC. SELDI-TOF MS serum profiling also is able to distinguish LSCC patients with or without lymph node metastasis.     

Targeting Jak/Stat pathway as a therapeutic strategy against SP/CD44+ tumorigenic cells in Akt/β-catenin-driven hepatocellular carcinoma

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Regeneration Defects in Yap and Taz Mutant Mouse Livers Are Caused by Bile Duct Disruption and Cholestasis

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