Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells.

Aim: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin) or the novel anticancer agents sorafenib or bortezomib.

Methods: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes.

Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma.

Background/aim: Treatment options of advanced cholangiocarcinoma (CC) are unsatisfactory and new therapeutic approaches are mandatory. Dysregulations of the mitogen-activated kinase (MAPK) pathway associated with proliferative advantages of tumors are commonly observed in CCs. The novel multi-kinase inhibitor sorafenib potently suppresses the growth of various cancers by inhibiting kinases of wild-type B-Raf, mutant(V559E)B-Raf and C-Raf but its effects on CC remains to be explored.

Antiproliferative and proapoptotic effects of histone deacetylase inhibitors on gastrointestinal neuroendocrine tumor cells.

Treatment options of advanced neuroendocrine tumors (NETs) are unsatisfactory. Hence, innovative therapeutic approaches are urgently needed. Inhibition of histone deacetylases (HDACs) is a promising new approach in cancer therapy.

Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer.

Aim: To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor (IGF-1R) tyrosine kinase inhibitor (TKI) NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer (CRC).

Methods: Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet staining were used for analysis of growth factor receptor protein expression and detection of cell number changes, respectively.

Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer.

Aim: To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma (HCC).

Methods: Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting.

Results: Erlotinib treatment inhibited the mitogen activated protein (MAP)-kinase pathway and signal transducer of activation and transcription (STAT)-mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology.

The insulin-like growth factor receptor 1 is a promising target for novel treatment approaches in neuroendocrine gastrointestinal tumours.

Gastrointestinal neuroendocrine tumours (NET) represent a heterogeneous tumour entity. The anti-neoplastic therapy of advanced NET disease is still unsatisfactory and innovative therapeutic approaches are needed. As NET frequently express insulin-like growth factors (IGFs) and their receptors (IGFR), known to promote survival, oncogenic transformation, tumour growth and spreading, the inhibition of the IGF/IGF-receptor system may offer possibilities for novel targeted treatment strategies of NET.

Blockade of IGF-1 receptor tyrosine kinase has antineoplastic effects in hepatocellular carcinoma cells.

Unlabelled: Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Most HCCs express insulin-like growth factors and their receptors (IGF-R).

EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer.

Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. In light of the very poor 5 year survival new therapeutic approaches are mandatory. Several reports indicate that the epidermal growth factor receptor (EGFR) is expressed frequently in HCC, most likely contributing to the aggressive growth characteristics of these tumors.

Targeting the epidermal growth factor receptor by erlotinib (Tarceva) for the treatment of esophageal cancer.

Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Because of very poor 5-year survival new therapeutic approaches are mandatory. Erlotinib (Tarceva), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors but its effect on esophageal carcinoma, known to express EGFR, remains unexplored.

Cell cycle arrest and apoptosis induction in hepatocellular carcinoma cells by HMG-CoA reductase inhibitors. Synergistic antiproliferative action with ligands of the peripheral benzodiazepine receptor.

Background/aims: Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer deaths worldwide. Inhibitors of cholesterol biosynthesis ('statins') have been proposed as promising adjunctive anticancer agents to treat HCC, but their mode of action is yet poorly characterized. We additionally investigated the potential benefit of a combination of peripheral benzodiazepine receptor (PBR) ligands and statins.

Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics.

Background/aims: Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. In light of the very poor 5-year-survival new therapeutic approaches are urgently needed. Recently, evidence has been accumulated that the epidermal growth factor receptor (EGFR) is a promising target for cancer therapy.

Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma.

Background/aims: Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Gefitinib, an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors, but its effect on HCC remains unexplored.

A novel approach in the treatment of neuroendocrine gastrointestinal tumors: additive antiproliferative effects of interferon-gamma and meta-iodobenzylguanidine.

Background: Therapeutic options to effectively inhibit growth and spread of neuroendocrine gastrointestinal tumors are still limited. As both meta-iodobenzylguanidine (MIBG) and interferon-gamma (IFNgamma) cause antineoplastic effects in neuroendocrine gastrointestinal tumor cells, we investigated the antiproliferative effects of the combination of IFNgamma and non-radiolabeled MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells.

Methods And Results: IFNgamma receptors were expressed in both models.