Tamoxifen enhances therapeutic effects of gemcitabine on cholangiocarcinoma tumorigenesis

Gu, Jie; Yuan, Kaiyu; Turk, Amy N.; Jhala, Nirag; Arnoletti, J. Pablo; Zhang, Kui; McDonald, Jay M.; Chen, Yabing

doi:10.1038/labinvest.2011.60

Cited by 14 publications

(8 citation statements)

References 54 publications

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“…Besides patho-physiological studies [106–113], this model is suitable for testing the efficacy of novel therapeutic approaches for CCA. Molecules like tannic acid, resveratrol, caffeic acid, anandamide, tamoxifen, felodipine, melatonin, and clobenpropit were shown to inhibit CCA xenograft tumour growth as did hematoporphyrin derivative-mediated photodynamic therapy, and oncolytic gene therapy,[114–126]. Similarly, targeting CCA cells with Slug si-RNA increased tumour sensitivity to cisplatin [127].…”

Section: Experimental Models Of Ccamentioning

confidence: 99%

Liver carcinogenesis: Rodent models of hepatocarcinoma and cholangiocarcinoma

Minicis¹,

Kisseleva²,

Francis³

et al. 2013

Digestive and Liver Disease

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Hepatocellular carcinoma and cholangiocarcinoma are primary liver cancers, both represent a growing challenge for clinicians due to their increasing morbidity and mortality. In the last few years a number of in vivo models of hepatocellular carcinoma and cholangiocarcinoma have been developed. The study of these models is providing a significant contribution in unveiling the pathophysiology of primary liver malignancies. They are also fundamental tools to evaluate newly designed molecules to be tested as new potential therapeutic agents in a pre-clinical set. Technical aspects of each model are critical steps, and they should always be considered in order to appropriately interpret the findings of a study or its planning. The purpose of this review is to describe the technical and experimental features of the most significant rodent models, highlighting similarities or differences between the corresponding human diseases. The first part is dedicated to the discussion of models of hepatocellular carcinoma, developed using toxic agents, or through dietary or genetic manipulations. In the second we will address models of cholangiocarcinoma developed in rats or mice by toxin administration, genetic manipulation and/or bile duct incannulation or surgery. Xenograft or syngenic models are also proposed.

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Section: Experimental Models Of Ccamentioning

confidence: 99%

Liver carcinogenesis: Rodent models of hepatocarcinoma and cholangiocarcinoma

Minicis¹,

Kisseleva²,

Francis³

et al. 2013

Digestive and Liver Disease

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“…We and others have found that activating intrinsic apoptotic signaling pathways using gemcitabine (26), doxorubicin (27) or ionizing radiation (28), sensitizes resistant cancer cells to death receptors-induced apoptosis. These intrinsic apoptotic activators function via inducing mitochondria leakage or DNA damage (26-28). …”

Section: Introductionmentioning

confidence: 99%

PARP-1 Regulates Resistance of Pancreatic Cancer to TRAIL Therapy

Yuan

Sun

Zhou

et al. 2013

Clinical Cancer Research

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Purpose Activating extrinsic apoptotic pathways targeting death receptors (DR) using agonistic antibodies or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer therapy. However, most pancreatic cancers are resistant to TRAIL therapy. The present studies aimed to identify combination therapies that enhance the efficacy of TRAIL therapy; and to investigate the underlying mechanisms. Experimental Design A xenograft model in nude mice was used to determine pancreatic cancer tumorigenesis and therapeutic efficacy of TRA-8, a monoclonal agonistic antibody for DR5. Pancreatic cancer cells were used to characterize mechanisms underlying poly(ADP-ribose) polymerase-1 (PARP-1) in regulating TRA-8-induced apoptosis in vitro. Results PARP-1 was found highly expressed in the TRA-8-resistant PANC-1 and Suit-2 cells, compared with TRA-8-sensitive BxPc-3 and MiaPaca-2. Inhibition of PARP-1 with a pharmacologic inhibitor sensitized PANC-1 and Suit2 cells to TRA-8 induced apoptosis in a dose-dependent manner. Furthermore, small interfering RNAs specifically knocking down PARP-1 markedly enhanced TRA-8-induced apoptosis in vitro, and augmented the efficacy of TRA-8 therapy on tumorigenesis in vivo. PARP-1 knockdown increased TRA-8-induced activation of caspase-8 in the death-induced signaling complex (DISC). Immuoprecipitation with DR5 antibody identified the recruitment of PARP-1 and PARP-1-mediated protein poly-ADP-ribosylation(pADPr) modification in the DR5-associated DISC. Further characterization revealed that PARP-1-mediated pADPr modification of caspase-8 inhibited caspase-8 activation, which may contribute to its function in regulating TRA-8 resistance. Conclusions Our studies not only provide novel molecular insights into the function of PARP-1 in regulating the extrinsic apoptosis machinery, but also support interventions combining PARP-1 inhibitors with death receptor agonists for pancreatic cancer therapy.

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“…Tamoxifen treatment induces apoptosis of breast cancer cells (19), cholangiocarcinoma cells (20) and rhabdomyosarcoma cells (21) at least in part through induction of caspase-3 activity. The stimulation of apoptosis by tamoxifen has been described in a number of tissues and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%