Sudden elevation of liver enzymes in a 64-year-old patient: a case report

Eradication of Helicobacter pylori usually consists of a 7-day course of triple therapy including metronidazole or amoxicillin plus clarithromycin plus a proton pump inhibitor. We report about a rare adverse event of Hp eradication in a patient with moderate chronic and moderate active pangastritis. Shortly after the end of treatment cholestatic hepatitis occurred which was most likely related to clarithromycin, perhaps enhanced by amoxicillin. Since liver dysfunction was self-limited, no further treatment was required. In summary, clinicians should be aware about the presented rare adverse event of Helicobacter pylori eradication treatment for a close monitoring of those patients and rapid management of acute liver failure

Association of Common Polymorphisms in GLUT9 Gene with Gout but Not with Coronary Artery Disease in a Large Case-Control Study

BACKGROUND: Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study. METHODS AND FINDINGS: First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region. CONCLUSION: Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population

Safety and Efficacy of Sunitinib in Patients with Unresectable Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (PNETs) are becoming increasingly common, with the majority of patients presenting with either lymph node involvement or metastatic disease, thus requiring systemic therapy. Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth rather than by simply interfering with rapidly dividing cells (eg, with traditional chemotherapy). In this review article, pharmacologic inhibition of multiple targets including vascular endothelial growth factor receptor (VEGF-R), platelet-derived growth factor receptor (PDGF-R), stem cell factor receptor (c-KIT-R), FML-like tyrosine kinase-3 receptor (FLT3-R), colony stimulating factor 1 receptor (CSF1-R), and glial cell-line derived neurotrophic factor receptor (RET-R) with sunitinib in patients with unresectable PNETs is discussed. Phase III data indicate that additional treatment with sunitinib can improve prognosis in these patients

Polo-like Kinase 1 Inhibition as a New Therapeutic Modality in Therapy of Cholangiocarcinoma

Background: Cholangiocarcinoma (CC) is highly resistant to chemotherapy and radiation, and is, therefore, difficult to cure. Polo-like kinases (Plks) are increasingly recognized as key regulators of mitosis, meiosis and cytokinesis. Alterations in PLK1- expression have been brought into relation with tumorigenesis, thus rendering PLK1 suppression an interesting target for tumor therapy. BI 2536, the first compound of the chemical class of dihydropteridinones, is a highly selective and potent inhibitor of PLK1. Materials and Methods: Retardation of cell proliferation by BI 2536 was tested in 14 CC cell lines by cell viability assay. Moreover, molecular activity of BI 2536 was investigated by Western blot, flow cytometry and real time- polymerase chain reaction (RT-PCR). Apposition of gemcitabine, 5-fluorouracil (5-FU) and insulin-like growth factor-1 receptor (IGF-1R) retardant NVP-AEW541 was also examined. Results: BI 2536 subdued proliferation in all CC cell lines, however, reaction was stronger in gallbladder carcinoma. Therapy with BI 2536 did not result in a significant change in phosphorylation of histone H3, AKT, and p42/44. However, exposure of cells to this compound caused arrest at the G2/M checkpoint and a surge in apoptosis. Moreover, PLK1 and FOXM1 were concurrently present in all cell lines, proposing a role for their involvement. Use of a mixture of BI 2536 with 5-FU or NVP-AEW541 resulted in synergism, while a mixture with gemcitabine resulted in additive activity. Conclusion: These experiments indicate that BI 2536 is effective against CC and increases the potency of 5-FU and NVP-AEW541

Treatment of biliary tract cancer with NVP-AEW541: Mechanisms of action and resistance

AIM: To investigate in vitro treatment with NVP-AEW541, a small molecule inhibitor of insulin-like growth factor-1 receptor (IGF-1R), in biliary tract cancer (BTC), since this disease is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and radiotherapy. METHODS: Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell counting. In addition, the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting, cell cycle analysis and reverse transcription-polymerase chain reaction (RT-PCR). Anti-tumoral drug effect in combination with gemcitabine, 5-fluorouracil (5-FU) and Polo-like kinase 1 inhibitor BI2536 was also studied. RESULTS: In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines, however response was lower in gallbladder cancer. Treatment with NVP-AEW541 was associated with dephosphorylation of IGF-1R and AKT. In contrast, phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently downregulated. In addition, treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 peak. Moreover, IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR, suggesting an autocrine loop of tumor cell activation. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combination with 5-FU or BI 2536 were only additive. CONCLUSION: Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine

Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors

AIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer

Neoadjuvant Down-Sizing of Hilar Cholangiocarcinoma with Photodynamic Therapy—Long-Term Outcome of a Phase II Pilot Study

Hilar cholangiocarcinoma (CC) is non-resectable in the majority of patients often due to intrahepatic extension along bile duct branches/segments, and even after complete resection (R0) recurrence can be as high as 70%. Photodynamic therapy (PDT) is an established palliative local tumor ablative treatment for non-resectable hilar CC. We report the long-term outcome of curative resection (R0) performed after neoadjuvant PDT for downsizing of tumor margins in seven patients (median age 59 years) with initially non-resectable hilar CC. Photofrin® was injected intravenously 24–48 h before laser light irradiation of the tumor stenoses and the adjacent bile duct segments. Major resective surgery was done with curative intention six weeks after PDT. All seven patients had been curatively (R0) resected and there were no undue early or late complications for the neoadjuvant PDT and surgery. Six of seven patients died from tumor recurrence at a median of 3.2 years after resection, the five-year survival rate was 43%. These results are comparable with published data for patients resected R0 without pre-treatment, indicating that neoadjuvant PDT is feasible and could improve overall survival of patients considered non-curatively resectable because of initial tumor extension in bile duct branches/segments—however, this concept needs to be validated in a larger trial