The direct CP violation parameter Re(epsilon'/epsilon) has been measured from the decay rates of neutral kaons into two pions using the NA48 detector at the CERN SPS. The 2001 running period was devoted to collecting additional data under varied conditions compared to earlier years (1997-1999). The new data yield the result: Re(epsilon'/epsilon) = (13.7 +/- 3.1) x 10(-4). Combining this result with that published from the 1997, 98 and 99 data, an overall value of Re(epsilon'/epsilon) = (14.7 +/- 2.2) x 10(-4) is obtained from the NA48 experiment. (C) 2002 Elsevier Science B.V. All rights reserved

0370-2693r99r$ -see front matter q 1999 Elsevier Science B.V. All rights reserved.Ž . PII: S 0 3 7 0 -2 6 9 3 9 9 0 1 0 3 0 -8 ( ) V. Fanti et al.r Physics Letters B 465 1999 335-348 336 A.

Tumor cell resistance to ionizing radiation and chemotherapy is a major obstacle in cancer therapy. One factor contributing to this is integrin-mediated adhesion to ECM. The adapter protein particularly interesting new cysteine-histidine-rich 1 (PINCH1) is recruited to integrin adhesion sites and promotes cell survival, but the mechanisms underlying this effect are not well understood. Here we have shown that PINCH1 is expressed at elevated levels in human tumors of diverse origins relative to normal tissue. Furthermore, PINCH1 promoted cell survival upon treatment with ionizing radiation in vitro and in vivo by perpetuating Akt1 phosphorylation and activity. Mechanistically, PINCH1 was found to directly bind to protein phosphatase 1α (PP1α) -an Akt1-regulating protein -and inhibit PP1α activity, resulting in increased Akt1 phosphorylation and enhanced radioresistance. Thus, our data suggest that targeting signaling molecules such as PINCH1 that function downstream of focal adhesions (the complexes that mediate tumor cell adhesion to ECM) may overcome radio-and chemoresistance, providing new therapeutic approaches for cancer.

The beam and detector, used for the NA48 experiment, devoted to the measurement of Re(epsilon'/epsilon) and for the NA48/1 experiment on rare KS and neutral hyperon decays, are described

Cancer stem cells (CSC) have the unique ability to cause tumor recurrences if they survive treatment. Radiotherapy has curative potential because it has been functionally shown to sufficiently inactivate CSCs. It is well known that CSCs mediate the radiation resistance of tumors by tumor-specific factors, such as the pretreatment number of CSCs and repopulation or reoxygenation during fractionated radiotherapy. CSCs appear to have a higher intrinsic radioresistance than non-CSCs, a factor that is especially important for the development of predictive biomarkers that, if this finding holds true, can only be successfully established if they are stem-cell specific. Recent clinical data imply that stem-cell-related surface markers may be directly used as predictors for the radiocurability of tumors with comparable risk factors, such as histology and size. Future studies need to address the question of which additional markers need to be considered if more heterogeneous patient collectives are investigated. With the goal of developing a direct targeting approach, investigators are currently evaluating several drugs that are intended to target CSCs by inhibiting stem-cellrelated signal transduction pathways. We need to preclinically test such drugs as combined-modality therapies in combination with radiotherapy to evaluate their curative potential, and optimize them by increasing their specificity to CSCs over normal tissue stem cells to avoid increased radiation toxicity.