Novel systemic treatment for hepatocellular carcinoma: a step-by-step review of current indications

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the main cause of cancer-related death worldwide. The available treatment options for HCC include liver transplant, locoregional therapy (such as ablation, embolization, and radiotherapy), and systemic treatment. The latter encompasses targeted therapy, immunotherapy, and angiogenesis inhibitors, alone or in combination. The introduction of immune checkpoint inhibitors and targeted drug therapy has been one of the most significant advances in HCC treatment. These therapies were shown to prolong overall survival and progression-free survival in clinical trials including patients with advanced HCC. In recent years, the systemic treatment of advanced HCC has vastly improved, with a median survival of 19.2 months in the IMbrave150 trial. However, further research is needed to determine the optimal sequence of treatment

Novel systemic treatment for hepatocellular carcinoma: a step-by-step review of current indications

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the main cause of cancer-related death worldwide. The available treatment options for HCC include liver transplant, locoregional therapy (such as ablation, embolization, and radiotherapy), and systemic treatment. The latter encompasses targeted therapy, immunotherapy, and angiogenesis inhibitors, alone or in combination. The introduction of immune checkpoint inhibitors and targeted drug therapy has been one of the most significant advances in HCC treatment. These therapies were shown to prolong overall survival and progression-free survival in clinical trials including patients with advanced HCC. In recent years, the systemic treatment of advanced HCC has vastly improved, with a median survival of 19.2 months in the IMbrave150 trial. However, further research is needed to determine the optimal sequence of treatment

Running performance at high running velocities is impaired but V'O_{2max} and peripheral endothelial function are preserved in IL-6^{−/−} mice

It has been reported that IL-6 knockout mice (IL-6^{−/−}) possess lower endurance capacity than wild type mice (WT), however the underlying mechanism is poorly understood. The aim of the present work was to examine whether reduced endurance running capacity in IL-6^{−/−} mice is linked to impaired maximal oxygen uptake (V′O_{2max}), decreased glucose tolerance, endothelial dysfunction or other mechanisms. Maximal running velocity during incremental running to exhaustion was significantly lower in IL-6−/− mice than in WT mice (13.00±0.97 m.min^{-1} vs. 16.89±1.15 m.min^{-1}, P<0.02, respectively). Moreover, the time to exhaustion during running at 12 m.min^{-1} in IL-6^{−/−} mice was significantly shorter (P<0.05) than in WT mice. V′O_{2max} in IL-6^{−/−} (n = 20) amounting to 108.3±2.8 ml.kg^{-1}.min^{-1} was similar as in WT mice (n = 22) amounting to 113.0±1.8 ml.kg^{-1}.min^{-1}, (P = 0.16). No difference in maximal COX activity between the IL-6^{−/−} and WT mice in m. soleus and m. gastrocnemius was found. Moreover, no impairment of peripheral endothelial function or glucose tolerance was found in IL-6^{−/−} mice. Surprisingly, plasma lactate concentration during running at 8 m.min−1 as well at maximal running velocity in IL-6^{−/−} mice was significantly lower (P<0.01) than in WT mice. Interestingly, IL-6^{−/−} mice displayed important adaptive mechanisms including significantly lower oxygen cost of running at a given speed accompanied by lower expression of sarcoplasmic reticulum Ca^{2+}-ATPase and lower plasma lactate concentrations during running at submaximal and maximal running velocities. In conclusion, impaired endurance running capacity in IL-6^{−/−} mice could not be explained by reduced V′O_{2max}, endothelial dysfunction or impaired muscle oxidative capacity. Therefore, our results indicate that IL-6 cannot be regarded as a major regulator of exercise capacity but rather as a modulator of endurance performance. Furthermore, we identified important compensatory mechanism limiting reduced exercise performance in IL-6^{−/−} mice

Bogactwo i bieda: próba refleksji humanistycznej

Ze wstępu: "Niniejsza książka jest efektem pracy zespołu realizującego program badań „Bogactwo i bieda - postawy, opinie, zachowania (badania w środowisku studentów Akademii Górniczo- Hutniczej)” w ramach grantu uczelnianego (G. U. Z. 10.430). Projekt ten nawiązuje do tradycji badań środowiska studenckiego AGH, które zapoczątkował przed laty profesor Julian Bugiel. Prezentowana praca tworzy pewną całość wraz z wątkami problemowymi realizowanych wcześniej badań: w latach 2000-2001 „Agresja i przemoc - postawy, opinie, zachowania (badania w środowisku studentów AGH)” (G. U. Z. 21.10.430.69), jak również z badaniami przeprowadzonymi w roku 2002 „Tolerancja i nietolerancja - postawy, opinie, zachowania (badania w środowisku studentów AGH)” (G. U. Z. 21.10.430.48)."(...

Formation of a quasicrystalline phase in Al–Mn base alloys cast at intermediate cooling rates

Al-rich 94Al–6Mn and 94Al–4Mn–2Fe alloys were suction-cast to evaluate thefeasibility of obtaining bulk quasicrystal-strengthened Al-alloys at intermediatecooling rates alloyed with non-toxic, easily accessible and affordable additions.The influence of different cooling rates on the potential formation of a quasicrystallinephase was examined by means of scanning and transmissionelectron microscopy, X-ray diffraction and differential scanning calorimetry.Increased cooling rates in the thinnest castings entailed a change in samplephase composition. The highest cooling rates turned out to be insufficient toform an icosahedral quasicrystalline phase (I-phase) in the binary alloy. Instead,an orthorhombic approximant phase occurred (L-phase). The addition of Fe tothe 94Al–6Mn binary alloy enhanced the formation of a quasicrystalline phase.At intermediate cooling rates of 102–103 K/s, various metastable phases wereformed, including decagonal and icosahedral quasicrystals and their approximants.Rods (1 mm in diameter) composed of I-phase particles embedded in Almatrix exhibited a hardness of 1.5 GPa, much higher than the 1.1 GPa of 94Al–6Mn