Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086–1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan–Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts

Cellular acidosis in rodents exposed to cadmium is caused by adaptation of the tissue rather than an early effect of toxicity

Proton (1H ) Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the biochemical response of bank voles and wood mice (two wild rodent species that are frequently found on metal-contaminated sites) to chronic cadmium (Cd) insult. Similar effects, in terms of both metabolic changes (consistent with cellular acidosis) and induced metallothionin (MT) production were observed in all animals. These changes appeared to be an adaptation of the liver to toxic insult rather than onset of a toxic effect, and, in common with previous studies, were more marked in bank voles than wood mice in common with previous studies. This may have reflected the greater Cd intake and assimilation of the former but was not explained by differences in concentrations of free (non MT-bound) Cd; concentrations of which were negligible in voles and mice. Responses to Cd insult were detected in both species even though their bodies contained cadmium concentrations well below the World Health Organisation critical renal concentration of 200 μg/g dry weight

Search for sequential heavy leptons in e+e- collisions at √s¯=52 GeV

We have searched for new sequential heavy leptons L± in e+e- collisions at √s =52 GeV using the TOPAZ detector at the KEK storage ring TRISTAN. In the collected data with an integrated luminosity of 3.6 pb-1, no evidence for L± production has been observed. A lower mass limit for L± is determined to be 25.5 GeV/c2 at 95% confidence level

Search for Top Quark in e+e- Collisions at sqrt[s]=52 GeV

We searched for possible signatures of top-quark production in 508 e+e- hadronic annihilation events collected at sqrt[s]=52 GeV by the TOPAZ detector at the KEK e+e- collider TRISTAN. The observed hadronic cross section and shape of hadronic events are consistent with the standard-model predictions without top quarks. A lower limit (95% confidence level) on the mass of the lightest top meson is set at 25.8 GeV