Epigallocatechin-gallate modulates chemotherapy-induced apoptosis in human cholangiocarcinoma cells.

Background: Green tea polyphenols are chemopreventive in several cancer models but their use as adjunctive therapeutic agents for cancer is unknown.

Aims: Cholangiocarcinomas respond poorly to chemotherapeutic agents and our aims were to assess the utility of green tea polyphenols as adjuncts to chemotherapy for cholangiocarcinoma.

Materials And Methods: We assessed the effect of purified green tea catechins on chemotherapy-induced apoptosis in KMCH, CC-LP-1 and Mz-ChA-1 human cholangiocarcinoma cells, and on chemosensitivity of Mz-ChA-1 cell xenografts in nude mice.

MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer.

Background And Aims: microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression negatively. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNA to tumor biology has not been established.

Methods: We evaluated the expression of miRNA in human hepatocellular cancer (HCC) by expression profiling, and defined a target gene and biologically functional effect of an up-regulated miRNA.

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

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 MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes.

The inflammation-associated cytokine interleukin-6 (IL-6) can contribute to tumor growth and resistance to therapy by the activation of survival mechanisms. In several human cancers, IL-6-activated survival signaling involves the signal transducers and activators of transcription (Stat) factors or protein kinase cascades. microRNAs (miRNAs) are endogenous regulators of gene expression that are altered in expression in many cancers.

Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression.

The association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. IL-6 can regulate the activity of DNA methyltransferases, and moreover, aberrant DNA methylation can contribute to carcinogenesis.

Tannic acid synergizes the cytotoxicity of chemotherapeutic drugs in human cholangiocarcinoma by modulating drug efflux pathways.

Background/aims: Tannic acid is an orally active plant polyphenol with potential for use as an anti-cancer agent for cholangiocarcinoma. To determine the potential use of tannic acid as an adjunct therapy, we sought to evaluate the interaction between tannic acid and chemotherapeutic agents.

Methods: Cytotoxicity was assessed in malignant human cholangiocytes.

Pifithrin-alpha enhances chemosensitivity by a p38 mitogen-activated protein kinase-dependent modulation of the eukaryotic initiation factor 4E in malignant cholangiocytes.

Pifithrin-alpha is the lead compound for a novel group of small molecules that are being developed for use as anticancer agents. The eukaryotic initiation factor 4E (eIF-4E) is overexpressed in many cancers, it can mediate sensitivity to therapy, and it may be regulated by p53. We examined the utility of pifithrin-alpha as an adjunct to therapy for the treatment of human cholangiocarcinoma, a tumor that is highly refractory to therapy, and we assessed the involvement of p53-dependent eIF-4E regulation in cellular responses to pifithrin-alpha.

Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines.

Background & Aims: Micro-RNA (miRNA) are endogenous regulatory RNA molecules that modulate gene expression. Alterations in miRNA expression can contribute to tumor growth by modulating the functional expression of critical genes involved in tumor cell proliferation or survival. Our aims were to identify specific miRNA involved in the regulation of cholangiocarcinoma growth and response to chemotherapy.

Effects of hardwood smoke exposure on allergic airway inflammation in mice.

Hardwood smoke (HWS) from wood burning stoves and fireplaces can be a significant contributor to the composition of ambient air pollution. We hypothesize that the inhalation of HWS by ovalbumin (OVA)-sensitized mice with preexisting lung inflammation leads to the exacerbation of allergic airway responses. Two different models were employed to characterize the effects of inhaled wood smoke on allergic airway inflammation.