Phase II and pharmacokinetic study of paclitaxel therapy for unresectable hepatocellular carcinoma patients

Chao, Yee; Chan, Wing Kai; Birkhofer, Martin; Hu, Oliver Yoa Pu; Wang, S. S.; Huang, Yi‐Hsiang; Liu, M.; Whang‐Peng, Jacqueline; H., K.; Lui, Wing‐Yiu; Lee, S. D.

doi:10.1038/bjc.1998.438

Cited by 112 publications

(64 citation statements)

References 21 publications

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“…[3][4][5] Sorafenib is a multikinase inhibitor of the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and Raf. It is the only agent that has been shown to improve overall survival and to be well tolerated in subjects with advanced-stage HCC with well-preserved liver function.…”

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confidence: 99%

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Kuwahara

Yamada

Egashira

et al. 2015

Biological & Pharmaceutical Bulletin

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The anti-tumor effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on several types of cancer cells have been reported. However, comparison of the anti-tumor effects of these drugs on human hepatocellular carcinoma (HepG2) cells has not been studied. We compared the anti-tumor effects of four SSRIs and two SNRIs on HepG2 cells. SSRIs and duloxetine dose-dependently decreased cell viability. Milnacipran had no effect on cell viability. The half-maximal inhibitory concentration was lower in the order of: sertraline, paroxetine, duloxetine, fluvoxamine, escitalopram, and milnacipran. Exposure to sertraline (2 µM) significantly increased caspase-3/7 activity. These results suggest that, of the agents tested here, sertraline had the highest sensitivity to HepG2 cells, and activation of the caspase pathway is involved in the anti-tumor effects of sertraline in HepG2 cells.Key words selective serotonin reuptake inhibitor; anti-tumor effect; sertraline; serotonin and norepinephrine reuptake inhibitor; human hepatocellular carcinoma cell Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancerbased death.

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confidence: 99%

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Kuwahara

Yamada

Egashira

et al. 2015

Biological & Pharmaceutical Bulletin

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“…Taxol, one of the antimicrotubule chemotherapeutic drugs, has been reported to be effective in the treatment of many tumours including ovarian, breast and lung cancers (Chabner, 1991;Rowinsky and Donehower, 1991;Slichenmyer and Von Hoff, 1991) but not in HCC (Chao et al, 1998). The well-established action mechanism of Taxol in the treatment of cancer is based on stabilisation of microtubules in tumour cells and induction of apoptosis.…”

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confidence: 99%

“…In addition, several signal transduction pathways such as Raf, JNK (Torres and Horwitz, 1998;Wang et al, 2000) and specific cell cycle phase (Lin et al, 1998) have been indicated to be involved in Taxol-elicited apoptotic responses. Moreover, expression of oncogenes or drug resistance factors as well as decoy receptors induction could account for the low response rate after chemotherapy in patients with HCC (Chao et al, 1998;Yamanaka et al, 2000), including Taxol treatment.…”

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Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway

Lin¹,

et al. 2003

Br J Cancer

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Hepatoma cells are known to be highly resistant to chemotherapy. Previously, we have found differential Taxol resistance in human and murine hepatoma cells. The aim of this study was to examine the effect of a multidrug resistance inhibitor, cyclosporin A in combination with Taxol on hepatoma in vitro and in vivo, and to identify the possible mechanism involved in Taxol resistance. Simultaneous treatment of cyclosporin A (0 -10 mM) and Taxol (0.1 mM) inhibited cell growth in vitro. Cyclosporin A interfered with Taxol (0.1 mM)-induced AKT activation and BAD phosphorylation. Cyclosporin A combined with Taxol treatment augments caspase-9, -3 activation and loss of mitochondrial membrane potential in HepG2 cells. PI3 kinase inhibitor, wortmannin, or a dominantnegative AKT1 expression vector treatment partially enhanced Taxol-induced apoptosis indicating that PI3 kinase-AKT pathway was involved in Taxol-resistance pathway. Moreover, combination treatment reduced tumour growth in SCID and C57BL/6 mice as compared to either Taxol or cyclosporin A treatment. Our results indicate that the combination of cyclosporin A and Taxol is effective in the reversal of Taxol resistance through the inhibition of PI3 kinase-AKT1 pathway.

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“…New chemotherapeutic drugs, such as paclitaxel, raltrexed, irinotecan, and nolatrexed, have not demonstrated encouraging results. These new drugs exhibit some antitumor activity, but response rates rarely exceed 10% (Rougier et al, 1997;Chao et al, 1998;O'Reilly et al, 1998;Stuart et al, 1999). The possible explanations for the refractioness of HCC to chemotherapy include tumor heterogeneity (Dexter and Leith, 1986), inadequate dosage of anticancer agents (Lai et al, 1990) and the inducible overexpression of the multidrug resistance gene (Huang et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma

2004

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of patients with HCC remain very poor. This study was conducted to evaluate the efficacy and safety of viscum fraxini-2 in patients with chemotherapy -naïve, advanced hepatocellular carcinoma. 23 patients with unrespectable HCC who had received no prior systemic chemotherapy with objectively measurable tumors were enrolled on this study. The mistletoe preparation for the study is an aqueous injectable solution. It contains one milliliter of viscum fraxini in dilution stage -2 (15 mg extract of 20 mg mistletoe herb from ash tree, diluted in di-natrium-mono-hydrogen phosphate, ascorbic acid and water) which is equivalent to 10 000 ng/ml injection ampoules. 2 ampoules of viscum fraxini -2 were administered subcutaneously once weekly. As assessed by conventional imaging criteria, 3 (13.1%) patients have achieved complete response, 2 (8.1%) patients have achieved a partial response. 9 (39.1%) had progressive disease while 9 (39.1%) patients didn't have evaluation of response due to early death. The median overall survival time for all patients was 5 months (range 2 -38 months), for those who achieved a CR was 29 months (range 12 -38 months) and, for those who achieved a PR was 6.5 months (range 6 -7 months). The median progression free survival for all patients was 2 months (range 1 -38 months), for those who achieved a CR, it was 29 months (range 8 -38 months) and for those who achieved a partial response, it was 5 months (range 4 -6 months). No hematologic toxicity has been encountered. The spectrum of non-hematologic toxicity was mild. The WHO toxicity criteria grade 3 -4 were 34.8% drug related fever, 13.1% erthyma at injection site and 17.4% pain at the site of injection. No drug related discontinuation or toxic deaths have occurred. Viscum fraxini-2 seems to be particularly promising in patients with advanced HCC, it shows antitumor activity and low toxicity profile. Further studies in combination with other active agents are clearly warranted.

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Phase II and pharmacokinetic study of paclitaxel therapy for unresectable hepatocellular carcinoma patients

Cited by 112 publications

References 21 publications

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway

Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma

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