Kostenvergleich zwischen zwei Kombinationstherapien gegen Hepatitis C mit pegylierten Interferonen und Ribavirin

Die Wirksamkeit und Sicherheit der beiden in der Schweiz zur Behandlung der Hepatitis C zugelassenen Kombinationstherapien (Pegasys®/Copegus®, PAC; PegIntron®/Rebetol®, PIR) ist sehr ähnlich. Das Ziel dieser Arbeit ist, die Kosten der beiden Therapien zu vergleichen und ihren kostengünstigsten Einsatz zu definieren. Die Durchschnittskosten für Genotyp-1-Patienten liegen zwischen CHF 21700.- (PAC) und CHF 19700.- (PIR), bzw. CHF 15600.- (PAC) und CHF 15000.- (PIR) für Genotyp-2/3-Patienten. Ein konsequenter Einsatz von PIR ist 9 bis 12% kostengünstiger als PAC. Weitere Kosteneinsparungen von 3% könnten bei einem Einsatz von PIR bei allen Patienten unter 85 kg (Genotyp 1) bzw. unter 75 kg (Genotyp 2/3) und von PAC bei solchen über 85 kg (Genotyp 1) bzw. über 75 kg (Genotyp 2/3) erreicht werden

Endoglycan plays a role in axon guidance by modulating cell adhesion

Axon navigation depends on the interactions between guidance molecules along the trajectory and specific receptors on the growth cone. However, our in vitro and in vivo studies on the role of Endoglycan demonstrate that in addition to specific guidance cue - receptor interactions, axon guidance depends on fine-tuning of cell-cell adhesion. Endoglycan, a sialomucin, plays a role in axon guidance in the central nervous system of chicken embryos, but it is neither an axon guidance cue nor a receptor. Rather, Endoglycan acts as a negative regulator of molecular interactions based on evidence from in vitro experiments demonstrating reduced adhesion of growth cones. In the absence of Endoglycan, commissural axons fail to properly navigate the midline of the spinal cord. Taken together, our in vivo and in vitro results support the hypothesis that Endoglycan acts as a negative regulator of cell-cell adhesion in commissural axon guidance

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Texas Student Medi

Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study

It is unknown whether sorafenib can be combined with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma. This study assesses the safety and tolerability of a continuous regimen of sorafenib combined with TACE

TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer.

Tumor budding in colorectal cancer is likened to an epithelial-mesenchymal transition (EMT) characterized predominantly by loss of E-cadherin and up-regulation of E-cadherin repressors like TWIST1 and TWIST2. Here we investigate a possible epigenetic link between TWIST proteins and the tumor budding phenotype. TWIST1 and TWIST2 promoter methylation and protein expression were investigated in six cell lines and further correlated with tumor budding in patient cohort 1 (n = 185). Patient cohort 2 (n = 112) was used to assess prognostic effects. Laser capture microdissection (LCM) of tumor epithelium and stroma from low- and high-grade budding cancers was performed. In colorectal cancers, TWIST1 and TWIST2 expression was essentially restricted to stromal cells. LCM results of a high-grade budding case show positive TWIST1 and TWIST2 stroma and no methylation, while the low-grade budding case was characterized by negative stroma and strong hypermethylation. TWIST1 stromal cell staining was associated with adverse features like more advanced pT (p = 0.0044), lymph node metastasis (p = 0.0301), lymphatic vessel invasion (p = 0.0373), perineural invasion (p = 0.0109) and worse overall survival time (p = 0.0226). Stromal cells may influence tumor budding in colorectal cancers through expression of TWIST1. Hypermethylation of the tumor stroma may represent an alternative mechanism for regulation of TWIST1

Investigation of IL-23 (p19, p40) and IL-23R identifies nuclear expression of IL-23 p19 as a favorable prognostic factor in colorectal cancer: a retrospective multicenter study of 675 patients.

IL-23 is a heterodimeric cytokine involved in inflammatory diseases; its role in cancer progression is controversial. Here we analyse the expression of IL-23 subunits (p40 and p19) and IL-23R in colorectal cancer with regard to disease progression, clinical-pathological and molecular aspects. Immunohistochemistry for IL-23p19, IL-23p40, IL-23R and CD8 was performed on a multi-punch tissue microarray of 195 colorectal cancers (cohort 1), matched normal tissue, adenoma and lymph node metastases. Results were compared with clinical-pathological features and CD8+ T-cell counts, then validated on two patient cohorts (cohort 2: n=341, cohort 3: n=139). Cytoplasmic/membranous expression of IL-23 (p19 and p40 subunits) and IL-23R, respectively were over-expressed in carcinomas versus adenomas and normal tissues (p<0.0001) but were reduced in lymph node metastases (p<0.0001). Nuclear IL-23p19 expression was observed in 23.1% and was associated with early TNM stage (p=0.0186), absence of venous (p=0.0124) and lymphatic invasion (p=0.01493), favorable survival (p=0.014) and absence of distant metastasis (p=0.0146; specificity: 100%). This unexpected cellular localization was confirmed by cell fractionation. The beneficial effect of nuclear IL-23p19 was restricted to tumours with CD8+ high counts. Results were validated on Cohorts 2/3. This multicenter study underlines the possible CD8(+)--dependency and beneficial effect of nuclear IL-23p19 on overall patient survival

Chronic Hepatitis C virus infection in Swiss primary care practices: low case loads-high barriers to treatment?

BACKGROUND: The primary care physician (PCP) diagnoses chronic Hepatitis C virus (HCV) infection in most patients. He serves as gatekeeper and plays a key role in counselling and treatment guidance. OBJECTIVES: To calculate the approximate HCV caseload per practice and characterize PCPs management of the disease; in particular, to determine antiviral treatment rates and reasons for PCPs for withholding treatment. The ultimate objective was to identify potentially modifiable barriers to treatment. METHODS: A confidential self-administered questionnaire centred on the above-mentioned questions was distributed to 2371 Swiss primary care physicians. All respondents of the main questionnaire received an additional small questionnaire focussed on the initial disease workup. Descriptive statistics were used to describe questionnaire responses and PCP demographics. RESULTS: The response rate was 53.1%. Of all participating PCPs (n = 1084), 86.2% reported having patients with chronic HCV, with an average number of 4 patients per practice; 18.6% (n = 142) of PCPs did not monitor their chronic HCV patients. Two-thirds (66.8%) of the sample chronic HCV patient population (n = 4626) never received antiviral therapy. The main reasons given by PCPs for withholding treatment were HCV-specialist advice, patient preference, normal liver enzymes and patient related factors like substance abuse or psychiatric co morbidity. CONCLUSIONS: Most PCPs follow patients with chronic hepatitis C, but practice caseloads are low, which may account for insecurity in managing this complex disease

Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes

Hepatitis C virus (HCV) infections are the major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. Both spontaneous and treatment-induced clearance of HCV depend on genetic variation within the interferon-lambda locus, but until now no clear causal relationship has been established. Here we demonstrate that an amino-acid substitution in the IFNλ4 protein changing a proline at position 70 to a serine (P70S) substantially alters its antiviral activity. Patients harbouring the impaired IFNλ4-S70 variant display lower interferon-stimulated gene (ISG) expression levels, better treatment response rates and better spontaneous clearance rates, compared with patients coding for the fully active IFNλ4-P70 variant. Altogether, these data provide evidence supporting a role for the active IFNλ4 protein as the driver of high hepatic ISG expression as well as the cause of poor HCV clearance