Antitumor effect of the nucleoside analogs 2-chlorodeoxyadenosine and 2′,2′-difluorodeoxycytidine on human hepatoma HepG2 cells

Talati

J. Gastrointest. Oncol.

2017

255

168

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis.The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.

Section: Gemcitabinementioning

confidence: 99%

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

Talati

J. Gastrointest. Oncol.

2017

255

168

American Journal of Physiology-Cell Physiology

“…The cytidine analogue gemcitabine is an effective chemotherapeutic drug for several gastrointestinal malignancies such as pancreatic cancer. Gemcitabine has been evaluated for use in HCC, with limited results but with manageable toxicity (15,38). Thus acquired chemoresistance is a likely cause for the observed clinical responses to this agent.…”

Section: Chemotherapeutic Stress Increases Angiogenesis In Tumorderivmentioning

confidence: 99%

Chemotherapeutic stress selectively activates NF-κB-dependent AKT and VEGF expression in liver cancer-derived endothelial cells

Meng¹,

Henson²,

Patel³

2007

Targeting endothelial cells (EC) that line tumor blood vessels forms the basis for metronomic therapy and is a promising new strategy for the treatment of cancer. Genetic and phenotypic differences between tumor-derived and normal ECs indicate that targeting tumor ECs may be therapeutically useful. In the present study, we examined differences in responses to chemotherapy in microvascular EC lines from tumoral (T-EC) and normal (N-EC) mouse liver tissues. The identity of these cells was confirmed by immunocytochemistry for EC markers, such as vascular endothelial-cadherin and CD31 for both types of ECs, and the tumor-endothelial-specific marker tumor endothelial marker-7 for T-EC. The involvement of Akt in NF-κB-dependent angiogenesis was different between N-EC and T-EC. Chemotherapeutic stress increased angiogenesis in T-EC, but not N-EC via an NF-κB-Akt-dependent manner. Both NF-κB and Akt were involved in enhanced survival and migration in T-EC in response to chemotherapeutic stress. Moreover, Akt was involved in NF-κB-dependent VEGF expression and angiogenesis. These studies, showing differences in cellular responses to chemotherapy in tumor-derived ECs, indicate that specific therapies targeting these cells may be therapeutically useful for liver cancers.

“…It is worth noting that Cladribine has been extensively evaluated in blood tumors but only very limited information is available regarding its possible use in nonhematological tumors. In this respect, a single study in a human carcinoma cell line (HepG2 cells) has been reported (Graziadei et al, 1998).…”

mentioning

confidence: 99%

A Key Role for Caspase-2 and Caspase-3 in the Apoptosis Induced by 2-Chloro-2′-deoxy-adenosine (Cladribine) and 2-Chloro-adenosine in Human Astrocytoma Cells

et al. 2003

Both the anticancer agent 2-chloro-2Ј-deoxy-adenosine (Cladribine) and its derivative 2-chloro-adenosine induce apoptosis of human astrocytoma cells (J Neurosci Res 60: 388 -400, 2000). In this study, we have analyzed the involvement of caspases in these effects. Both compounds produced a gradual and time-dependent activation of "effector" caspase-3, which preceded the appearance of the nuclear signs of apoptosis, suggesting a temporal correlation between these two events. Moreover, the caspase inhibitor N-benzyloxycarbonyl-