Preclinical antitumor efficacy of the polyamine analogue N1, N11-diethylnorspermine administered by multiple injection or continuous infusion

Certain N-alkylated analogues of the natural polyamine spermine have been found to disrupt polyamine pool homeostasis and inhibit tumor cell growth. The most effective of these analogues, N1, N11-diethylnorspermine (DENSPM), apparently depletes intracellular polyamine pools primarily by inducing the polyamine acetylating enzyme spermidine/spermine N1-acetyltransferase, which contributes to polyamine depletion via increased polyamine excretion and catabolism. In this report, the experimental therapeutic efficacy of DENSPM was further examined with the use of other human solid tumor xenografts, including A121 ovarian carcinoma, A549 lung adenocarcinoma, HT29 colon carcinoma, and SH-1 melanoma, and compared with previously obtained findings with MALME-3M and PANUT-3 human melanomas. In vitro studies indicated that the growth sensitivity of most tumor cell lines to DENSPM was similar, with characteristically flat dose-response curves and IC50s ranging between 0.1 and 1 micrometer the only exception was the HT29 colon carcinoma cell line, which had an IC50 of >100 micrometer. For in vivo studies, DENSPM was administered by i.p. injection to female nude athymic mice at 40 and/or 80 mg/kg 3 times a day (every 8 h) for 6 days or by continuous s.c. infusion with the use of Alzet pumps at 120, 240, or 360 mg/kg/day for 4 days. Treatment began after s.c. tumor xenografts had reached 100-200 mm3. The SH-1 melanoma, A549 lung adenocarcinoma, and A121 ovarian carcinoma xenografts responded well to the i.p. administration of analogue with obvious tumor regressions, long-term tumor growth suppressions, and a significant proportion (up to 40%) of apparent cures (i.e., lack of tumor regrowth). However, in similarity to in vitro findings, HT29 colon carcinoma xenografts responded poorly to DENSPM treatment. Massive induction of N1-acetyltransferase activity and extensive depletion of polyamine pools were consistent findings in most tumor types after in vivo or in vitro treatment with DENSPM. The rapidly growing human LOX melanoma xenograft, however, demonstrated poor induction of N1-acetyltransferase activity and the poorest response to DENSPM treatment. In nude athymic mice with MALME-3M melanoma xenografts, constant infusion delivery of DENSPM resulted in prolonged inhibition of tumor growth and long-term tumor regressions comparable to those produced by multiple i.p. injections. On the basis of the unique structure of DENSPM, novel target and mode of intervention, mild host toxicity, and activity against different human solid tumor xenografts, DENSPM is currently being developed as an antitumor agent in humans.     

Viewpoint on the Formation and Evolution of Annealing Twins During Thermomechanical Processing of FCC Metals and Alloys

Metallurgical and Materials Transactions A - The question of the formation mechanism of annealing twins in face-centered cubic metals and alloys, which is still not resolved in spite of the fact...     

An adaptive level‐set method with enhanced volume conservation for simulations in multiphase domains

Mechanical computations in multiphase domains raise numerous difficulties from the generation of the initial mesh to its adaptation throughout the simulation. All alternatives to mesh adaptation, such as level‐set methods, have the well‐known drawback of inducing volume conservation issues. In this paper, a moving mesh method is coupled to a topological mesh adaptation technique in order to track moving and deforming interfaces in multiphase simulations, with a robust control of mesh quality. Level‐set functions are used as intermediaries to enhance the mesh adaptation technique with a volume conservation constraint, which is compatible both with implicit and with body‐fitted interfaces. Results show that this method has the same advantage of permitting important displacements, deformations, and topological changes (coalescence of interfaces, for example) as a standard level‐set method, while volume diffusion is drastically reduced. Copyright © 2016 John Wiley & Sons, Ltd.     

Usefulness of computed tomography and scintigraphy in diagnosis of emphysematous bullae in the lung

The x-ray examinations usually do not reveal morbid changes after lung expansion in the treatment of spontaneous pneumothorax. In our observation computed tomography (CT) and scintigraphy enable not only the exact determination of the extent of changes but also they disclose bullae invisible in conventional chest radiographs. 15 patients with cured spontaneous pneumothorax and 10 patients with radiographic evidence of a bulla or bullae were examined. CT scans showed bullae from 3 to 18 cm in diameter involving predominantly the upper lobes. 4 patients had additionally subpleural or intraparenchymal bullae of various degrees. In all patients with cured spontaneous pneumothorax, CT scans revealed intraparenchymal bullae, and in 6 cases bilateral intraparenchymal bullae were revealed. Only in sites of large bullae, no isotopic marker or its low elimination was shown in perfusion and inhalation scintigraphy. 10 patients with giant bullous emphysema were operated; in 6 patients enucleation of bullae, in 3 lobectomy and in one patient bullectomy were performed. CONCLUSION: CT is a method of choice in the diagnosis of lung emphysematous bullae and it enables the detection of the changes undetectable in chest radiographs. Perfusion and inhalation scintigraphy is helpful in the diagnosis of large emphysematous bullae and postoperative follow-up examination.     

On robustness of camera identification algorithms

Multimedia Tools and Applications - In this paper we consider the problem of a privacy threat enabling tracing digital cameras by the analysis of pictures they produced. As thousands of images are...     

The dynamic properties of a single‐phase transformer‐based inverter for ups systems

This paper presents two algorithms for the creation of an analytical model of a single‐phase transformer‐based inverter, using either the measurements of the control frequency‐dependent characteristics of the inverter or the initial in‐circuit frequency‐dependent measurements of the transformer. The paper discusses how the parameters of the line transformer influence the dynamic properties of the inverter and, as a consequence, the design of the instantaneous control feedback loop. Line transformers, widely used in industry, have not yet been analysed for use at higher than normal operating frequencies. The basic parameters of the transformer are the nonlinear functions of the primary voltage amplitude and frequency. The paper includes verification of both methods using the breadboard experimental model. In the final step, the inverter control transfer functions are calculated. To show the utility of both models, an exemplary discrete controller for the experimental inverter model has been designed and tested. Copyright © 2015 John Wiley & Sons, Ltd.