Perspectives of immunotherapy in hepatocellular carcinoma (HCC).

Immunotherapy is considered a new treatment option for many tumor entities, as decades of research into cancer immunotherapy have recently yielded promising results. Indeed, impressive clinical results of checkpoint blockade inhibitors in malignant melanoma and non-small cell lung cancer indicate the therapeutic potential of tumor-specific immune restoration. Over the years, different immunotherapeutic approaches have been evaluated for the treatment of hepatocellular carcinoma (HCC) with some respectable results. In this review article, we will summarize the key studies of the past 30 years and will elucidate in which direction the dynamic field of HCC immunotherapy is currently moving.

[Perspectives on immunotherapy for hepatocellular carcinoma]. / Perspektiven für eine Immuntherapie beim hepatozellulären Karzinom.

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide with a high mortality. Available therapeutical options are limited, thus the development of new, innovative therapeutic strategies is crucial. Based on the immune system's antitumoral effect, immunotherapy is a promising new treatment option. Specific antitumoral T-cell responses can be detected in patients with HCC, however, their impact on tumor control seems to be rather weak. Various different immunosuppressive mechanisms seem to contribute to the failure of tumor-specific T-cell responses. Thus, the aim of immunotherapeutic strategies is to address these mechanisms of T-cell failure and to induce new or to boost existing antitumoral immune responses.

[EEG-adjusted target-controlled infusion : Propofol target concentration with different doses of remifentanil]. / EEG-adaptierte "target-controlled infusion" : Propofolzielkonzentration bei unterschiedlichen Remifentanildosierungen.

BACKGROUND: The aim of this study was to examine to what extent the use of electroencephalography (EEG) monitoring leads to an adaptation of the target-controlled infusion (TCI) concentration of propofol during propofol anaesthesia with different doses of remifentanil. PATIENTS AND METHODS: With ethics committee approval 60 patients (27-69 years old) with American Society of Anesthesiologists classification (ASA) I-III received anaesthestics with propofol (TCI, Diprifusor, AstraZeneca, Wedel, Deutschland) and 0.2, 0.4, or 0.6 microg/kg body weight remifentanil, respectively (groups 1-3). Anaesthesia was maintained at a level of deep hypnosis (EEG stages D(2)/E(0), EEG monitor: Narcotrend, version 2.0/5.0, manufacturer: MT MonitorTechnik, Bad Bramstedt, Germany). RESULTS: During the steady state the propofol concentration in groups 1-3 was 3.02+/-0.86, 1.93+/-0.53 and 1.60+/-0.55 microg/ml, respectively (p<0.001). Women had a higher propofol consumption than men (p<0.05). Dreams during anaesthesia were more often reported by women than by men (p<0.05). The need for postoperative analgesia decreased with an increasing intraoperative remifentanil dose (p<0.05). CONCLUSIONS: The study demonstrates that remifentanil has both analgetic and hypnotic effects. With increasing remifentanil dose the propofol requirement decreased and in this context EEG monitoring is useful to adapt the target concentrations of propofol to the patients' age and gender.

Oculomotor phenotypes in autosomal dominant ataxias.

OBJECTIVE: To quantify the oculomotor features of the common spinocerebellar ataxia (SCA) syndromes. SETTING: University ataxia clinic. PATIENTS: Twenty probands with documented SCA mutations. METHODS: Electro-oculographic recordings of saccadic, smooth pursuit, optokinetic, vestibular, and visual-vestibular eye movements. RESULTS: Distinct phenotype and genotype patterns were identified with modest overlap between patterns. Slowing of saccade peak velocities occurred only in SCA1 and SCA2, being present in 100% of patients with SCA2. Impaired vestibulo-ocular reflex gain occurred with SCA3 only. Patients with SCA6 had prominent deficits in smooth tracking but normal saccade velocities and vestibuloocular reflex gain. CONCLUSIONS: The oculomotor findings are consistent with pure cerebellar involvement in SCA6, pontine involvement in SCA1 and SCA2, and vestibular nerve or nuclei involvement in SCA3. These phenotypes can be useful for clinical diagnosis and for investigating the mechanism of system specificity with the SCA syndromes.

Direct modulation of Aplysia S-K+ channels by a 12-lipoxygenase metabolite of arachidonic acid.

Lipoxygenase metabolites of arachidonic acid have recently been shown to modulate the activity of ion channels in nerve and muscle cells. The mechanism of action of these metabolites is, however, unknown. In sensory neurons of Aplysia, the S-K- channel is under the dual modulatory control of 5-hydroxytryptamine (5-HT), which decreases the number of active S channels through cyclic AMP-dependent phosphorylation, and the neuropeptide FMRFamide, which increases the probability of S-channel opening through the 12-lipoxygenase metabolite 12-hydroperoxyeicosatetraenoic acid (12-HPETE). Here we report that the increase in the probability of S-channel opening with FMRFamide is mimicked by application of 12-HPETE to cell-free membrane patches that lack ATP and GTP. Thus, 12-HPETE can act directly to modulate S-channel activity, independently of protein phosphorylation or dephosphorylation, G-protein activation or cyclic nucleotides.