Predictions of survival up to 10 years after diagnosis for European women with breast cancer in 2000-2002

Few studies have addressed longer-term survival for breast cancer in European women. We have made predictions of 10-year survival for European women diagnosed with breast cancer in 2000-2002. Data for 114,312 adult women (15-99 years) diagnosed with a first primary malignant cancer of the breast during 2000-2002 were collected in the EUROCARE-4 study from 24 population-based cancer registries in 14 European countries. We estimated relative survival at 1, 5, and 10 years after diagnosis for women who were alive at some point during 2000-2002, using the period approach. We also estimated 10-year survival conditional on survival to 1 and 5 years after diagnosis. Ten-year survival exceeded 70% in most regions, but was only 54% in Eastern Europe, with the highest value in Northern Europe (about 75%). Ten-year survival conditional on survival for 1 year was 2-6% higher than 10-year survival in all European regions, and geographic differences were smaller. Ten-year survival for women who survived at least 5 years was 88% overall, with the lowest figure in Eastern Europe (79%) and the highest in the UK (91%). Women aged 50-69 years had higher overall survival than older and younger women (79%). Six cancer registries had adequate information on stage at diagnosis; in these jurisdictions, 10-year survival was 89% for local, 62% for regional and 10% for metastatic disease. Data on stage are not collected routinely or consistently, yet these data are essential for meaningful comparison of population-based survival, which provides vital information for improving breast cancer control. What's new? Policy-makers and health-care planners need accurate data on long-term survival to improve cancer control. This Europe-wide study of 10-year survival identified low survival in Eastern Europe for women with breast cancer in 2000-2002, and wide variation by age at diagnosis. Data on stage at diagnosis are crucial for meaningful comparison of population-based survival, and fundamental for improving breast cancer control, but our analyses confirmed that stage data are not collected routinely or consistently Copyright © 2012 UICC.

Ordering the cytochrome c-initiated caspase cascade:hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.

Millimeter-wave communications for 5G: fundamentals: Part I [Guest Editorial]

The widespread availability and demand for multimedia capable devices and multimedia content have fueled the need for high-speed wireless connectivity beyond the capabilities of existing commercial standards. While fiber optic data transfer links can provide multigigabit- per-second data rates, cost and deployment are often prohibitive in many applications. Wireless links, on the contrary, can provide a cost-effective fiber alternative to interconnect the outlining areas beyond the reach of the fiber rollout. With this in mind, the ever increasing demand for multi-gigabit wireless applications, fiber segment replacement mobile backhauling and aggregation, and covering the last mile have posed enormous challenges for next generation wireless technologies. In particular, the unbalanced temporal and geographical variations of spectrum usage along with the rapid proliferation of bandwidth- hungry mobile applications, such as video streaming with high definition television (HDTV) and ultra-high definition video (UHDV), have inspired millimeter-wave (mmWave) communications as a promising technology to alleviate the pressure of scarce spectrum resources for fifth generation (5G) mobile broadband.

The Kepler-10 Planetary System Revisited by HARPS-N: A Hot Rocky World and a Solid Neptune-Mass Planet

Kepler-10b was the first rocky planet detected by the Kepler satellite and confirmed with radial velocity follow-up observations from Keck-HIRES. The mass of the planet was measured with a precision of around 30%, which was
insufficient to constrain models of its internal structure and composition in detail. In addition to Kepler-10b, a second planet transiting the same star with a period of 45 days was statistically validated, but the radial velocities were only
good enough to set an upper limit of 20 M⊕ for the mass of Kepler-10c. To improve the precision on the mass for planet b, the HARPS-N Collaboration decided to observe Kepler-10 intensively with the HARPS-N spectrograph
on the Telescopio Nazionale Galileo on La Palma. In total, 148 high-quality radial-velocity measurements were obtained over two observing seasons. These new data allow us to improve the precision of the mass determination for Kepler-10b to 15%. With a mass of 3.33 ± 0.49 M⊕ and an updated radius of 1.47+0.03 −0.02 R⊕, Kepler-10b has a density of 5.8 ± 0.8 g cm−3, very close to the value predicted by models with the same internal structure and composition as the Earth. We were also able to determine a mass for the 45-day period planet Kepler-10c, with an even better precision of 11%. With a mass of 17.2 ± 1.9 M⊕ and radius of 2.35+0.09 −0.04 R⊕, Kepler-10c has a density of 7.1 ± 1.0 g cm−3. Kepler-10c appears to be the first strong evidence of a class of more massive solid planets with longer orbital periods

CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells

The surface marker CD44 has been identified as one of several markers associated with cancer stem cells (CSC) in solid tumors, but its ubiquitous expression in many cell types, including hematopoietic cells, has hindered its use in targeting CSCs. In this study, 28 paired primary tumor and adjacent nontumor gastric tissue samples were analyzed for cell surface protein expression. Cells that expressed pan-CD44 were found to occur at significantly higher frequency in gastric tumor tissues. We identified CD44v8-10 as the predominant CD44 variant expressed in gastric cancer cells and verified its role as a gastric CSC marker by limiting dilution and serial transplantation assays. Parallel experiments using CD133 failed to enrich for gastric CSCs. Analyses of another 26 primary samples showed significant CD44v8-10 upregulation in gastric tumor sites. Exogenous expression of CD44v8-10 but not CD44 standard (CD44s) increased the frequency of tumor initiation in immunocompromised mice. Reciprocal silencing of total CD44 resulted in reduced tumor-initiating potential of gastric cancer cells that could be rescued by CD44v8-10 but not CD44s expression. Our findings provide important functional evidence that CD44v8-10 marks human gastric CSCs and contributes to tumor initiation, possibly through enhancing oxidative stress defense. In addition, we showed that CD44v8-10 expression is low in normal tissues. Because CD44 also marks CSCs of numerous human cancers, many of which may also overexpress CD44v8-10, CD44v8-10 may provide an avenue to target CSCs in other human cancers.