Killing of tumor cells by cytotoxic therapies, such as chemotherapy or gamma-irradiation, is predominantly mediated by the activation of apoptotic pathways. Refractoriness to anticancer therapy is often due to a failure in the apoptotic pathway. The mechanisms that control the balance between survival and cell death in cancer cells are still largely unknown. Tumor cells have been shown to evade death signals through an increase in the expression of antiapoptotic molecules or loss of proapoptotic factors. We aimed to study the involvement of PED, a molecule with a broad antiapoptotic action, in human breast cancer cell resistance to chemotherapeutic drugs-induced cell death. We show that human breast cancer cells express high levels of PED and that AKT activity regulates PED protein levels. Interestingly, exogenous expression of a dominant-negative AKT cDNA or of PED antisense in human breast cancer cells induced a significant down-regulation of PED and sensitized cells to chemotherapy-induced cell death. Thus, AKT-dependent increase of PED expression levels represents a key molecular mechanism for chemoresistance in breast cancer. (Cancer Res 2005; 65(15): 6668-75)

Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were classified using grading and staging scores. Ultrasound-guided LB of focal lesions were excluded from this study. LB was performed on 1,318 outpatients and 263 hospitalized patients. The mean age of the hospitalized patients was higher than that of the outpatients (p < 0.0001). As major side effects, one death and one haemoperitoneum requiring blood transfusion were recorded in the hospitalized patients. As minor side effects, one haemorrhage occurred in the hospitalized patients, whereas a case of haemobilia and 2 cases of subcapsular haematoma were recorded in the outpatients. In both groups pain at the puncture site was the most frequent minor complication which easily resolved after non-steroid drug administration. Severe histological diagnoses, both in terms of grading and staging, were significantly associated with hospitalized patients. In conclusion, by carefully selecting patients and using prebiopsy ultrasound to assess the puncture site, outpatient LB can be safely performed in most cases; this procedure should be more widely used, because it has met with the favour of patients who are able to return home the same day and reduces public health care service costs.

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grading system, to the interpretation of the last Tumour-Nodes-Metastasis staging rules, and to identifying new markers of prognostic significance in clinical practice. A consensus was achieved on the main points. CONCLUSIONSThe 2004 WHO grading system must become acceptable to clinicians, perhaps by a minimal modification of the present terminology.Simple transurethral resection-biopsy should be expressed in terms of clinical rather than pathological staging. Although there are substantial improvements, no new markers can be recommended for routine use in histopathology at present.