Update on . . . the proteasome inhibitor PS341

The proteasome degradation system is one of the most efficient proteolytic process in living cells. We will focus here on a new compound, called PS341, which is the first proteasome inhibitor entering clinical phases. First results about its use in multiple myeloma or leukemic cells will be discussed.     

Radiotherapy of seminoma of the testis. Report on 129 patients.

From 1958 to 1974, 129 patients with pure seminoma of the testis were admitted to the Institute of Radiology, University of Florence. Sixty-two were in Stage I, 36 in Stage II A, 23 in Stage II B, 3 in Stage III, and 5 in Stage IV, Para-aortic and ipsilateral iliac nodes were treated in all cases with doses ranging from 3000 to 4200 rads. In the treatment of the supradiaphragmatic area, uniform criteria were not adopted. Out of 124 cases in Stage I, II A and B, and III, 17 suffered a replase; aall relapsed cases died except for one. Site and cause of the failures were analyzed. Prophylactic irradiation of the mediastinum and supraclavicular area appears to lower the probability of recurrence in Stage II. Doses over 3500 rads may be necessary to destroy large metastases. The presence of nonseminomatous areas in the seminoma showing inadequate regression after radiotherapy must be suspected; an exploratory laparotomy should be indicated in such a case.     

Putting the rap on Akt.

The protein kinase Akt is activated in a wide variety of cancers, and this activation results in enhanced resistance to apoptosis through multiple mechanisms. This article reviews the control of Akt activation by the opposing actions of the oncogene phosphoinositide 3-kinase (PI3-K) and the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10. The activation of Akt by transforming mutations, such as the amplification of HER-2/neu in breast cancer and the formation of the BCR/ABL fusion gene in chronic myelogenous leukemia, seems to be essential for the transforming activity of these oncogenes. We discuss several of the proposed mechanisms for the antiapoptotic effect of activated Akt, including the inhibition of the proapoptotic protein Bad, downregulation of death receptors, and enhancement of the glycolytic rate. Increased glycolysis is seen in many malignancies and forms the basis for the increasing use of positron emission tomography imaging for diagnosis and staging. Finally, we discuss rapamycin and its analogs, which are now in trials as antineoplastic therapy; these agents show particular promise in tumors in which Akt has been activated.     

Notes on the construction of solid-state detectors.

BACKGROUND AND PURPOSE: Solid-state detectors such as diodes and diamonds are useful radiation detectors, particularly for small field measurements, such as in stereotactic dosimetry or in the small sub-field measurements required for intensity modulated radiotherapy (IMRT) . In all small field measurements, positioning of the detector is critical. Generally it is assumed that the center of the sensitive volume of each solid-state detector is coincident with the geometric center of the outer casing. PATIENTS AND METHODS: X-rays were taken of four detectors (diamond, three types of diode) to determine the physical characteristics of each, particularly the position of the centre of the sensitive volume. RESULTS: The results showed that the position of the centre of the sensitive volume is not always coincident with the geometric centre of a solid-state detector. CONCLUSIONS: The construction of a detector used for precise measurements should be investigated prior to use, by taking high resolution x-ray images.