System integration and radiation pattern measurements of a phased array antenna employing an integrated photonic beamformer for radio astronomy applications

In this paper we describe the system integration and the experimental demonstration of a photonically beamformed four-element receiving array antenna for radio astronomy applications. To our knowledge, the work described here is the first demonstration of the squint-free, continuously tunable beamsteering capability offered by an integrated photonic beamformer based on optical ring resonator truetime-delay units, with measured radiation patterns. The integrated beamformer is realized in a low loss, complementary metal-oxide-semiconductor (CMOS) compatible optical waveguide technology. The measurements show a wideband, continuous beamsteering operation over a steering angle of 23.5 degrees and an instantaneous bandwidth of 500 MHz limited only by the measurement setup

Photonic integrated beamformers for broadband radio astronomy

For the modern radio astronomy instruments wide instantaneous bandwidth is a characteristic of great interest. This can be a difficult requirement for a phased array antenna (PAA)employing a traditional electronic beamformer: the performance of the constituting components, mainly combiners and delay elements, limits the bandwidth of the total system

Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib

Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of CECs in parallel with hematopoietic progenitor cells (HPCs) in the blood of renal cell cancer patients during sunitinib treatment. We analyzed the kinetics of a specific population of small VEGFR2-expressing CECs (CD45(neg)/CD34(bright)), HPCs (CD45(dim)/CD34(bright)), and monocytes in the blood of 24 renal cell cancer (RCC) patients receiving 50 mg/day of the multitargeted VEGF inhibitor sunitinib, on a 4-week-on/2-week-off schedule. Blood was taken before treatment (C1D1), on C1D14, C1D28, and on C2D1 before the start of cycle 2. Also plasma VEGF and erythropoietin (EPO) were determined. Remarkably, while CD34(bright) HPCs and monocytes decreased during treatment, CD34(bright) CECs increased from 69 cells/ml (C1D1) to 180 cells/ml (C1D14; P = 0.001) and remained high on C1D28. All cell populations recovered to near pre-treatment levels on C2D1. Plasma VEGF and EPO levels were increased on C1D14 and partly normalized to pre-treatment levels on C2D1. In conclusion, opposite kinetics of two circulating CD34(bright) cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused by sunitinib targeting of immature tumor vessel

Advanced glycation end products in human cancer tissues: detection of Nepsilon-(carboxymethyl)lysine and argpyrimidine

Tumors are generally characterized by an increased glucose uptake and a high rate of glycolysis. Since one consequence of an elevated glycolysis is the nonenzymatic glycation of proteins, we studied the presence of advanced glycation end products (AGEs) in human cancer tissues. We detected the presence of the AGEs N(epsilon)-(carboxymethyl)lysine (CML) and argpyrimidine in several human tumors using specific antibodies. Because AGEs have been associated with the etiology of a variety of different diseases, these results suggest that CML and argpyrimidine could be implicated in the biology of human cancer

The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor on the expression of thymidine phosphorylase

Thymidine phosphorylase (platelet-derived-endothelial-cell-growth-factor) catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate, activates 5′-deoxy-5-fluorouridine (5′DFUR) and inactivates trifluorothymidine (TFT). The effect of 5′DFUR and TFT with or without a specific thymidine phosphorylase inhibitor (TPI) on thymidine phosphorylase mRNA, protein expression and activity was studied, in three human colon cancer cell lines, WiDR, HT29 and Lovo exposed for 72 h at IC50 concentrations. In Lovo cells TFT plus TPI only increased thymidine phosphorylase-protein expression 1.7-fold; 5′DFUR and TFT treatment increased thymidine phosphorylase mRNA levels 5- and 1.4-fold, respectively. In WiDR cells, 5′DFUR plus TPI significantly decreased thymidine phosphorylase-protein. TFT and TFT plus TPI increased thymidine phosphorylase-protein 2- and 3-fold, respectively. TPI and 5′DFUR decreased thymidine phosphorylase-mRNA levels significantly. In HT29 cells, 5′DFUR and 5′DFUR plus TPI decreased both thymidine phosphorylase-protein and thymidine phosphorylase-mRNA. In all cell lines 5′DFUR and TFT did not affect thymidine phosphorylase activity, but treatment with TPI (alone or in combination) eliminated thymidine phosphorylase activity. This demonstrated that regulation is drug and cell line dependent

The use of perfusion CT for the evaluation of therapy combining AZD2171 with gefitinib in cancer patients

The purpose of this study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (CTP) in evaluating the hemodynamic response of tumors in the chest and abdomen treated with a combination of AZD2171 and gefitinib. Thirteen patients were examined just before and every 4-6 weeks after starting therapy. Following intravenous injection of a contrast agent, dynamic image acquisition was obtained at the level of a selected tumor location. To calculate perfusion, the maximum-slope method was used. Pre-treatment average perfusion for extra-hepatic masses was 84 ml/min/100 g, for liver masses arterial perfusion was 25 ml/min/100 g, and a portal perfusion of 30 ml/min/100 g was found. After the administration of AZD2171 and gefitinib, in extra-hepatic masses an initial decrease in perfusion of 18% was followed by a plateau and in liver masses an initial decrease of 39% within the lesions and of 36% within a rim region surrounding the lesions was followed by a tendency to recovery of hepatic artery flow. In conclusion, CTP is feasible in showing changes of perfusion induced by anti-angiogenic therapy

Argpyrimidine-modified Heat shock protein 27 in human non-small cell lung cancer: a possible mechanism for evasion of apoptosis

Tumors generally display a high glycolytic rate. One consequence of increased glycolysis is the non-enzymatic glycation of proteins leading to the formation of advanced glycation end-products (AGEs). Therefore, we studied the presence of AGEs in non-small cell lung cancer and consequences thereof. We show the presence of two AGEs, i.e. the major AGE N(epsilon)-(carboxymethyl)lysine (CML) and the methylglyoxal-arginine adduct argpyrimidine, in human non-small cell lung cancer tissues by immunohistochemistry. We found in squamous cell carcinoma and adenocarcinoma tissues a strong CML positivity in both tumour cells and tumour-surrounding stroma. In contrast, argpyrimidine positivity was predominantly found in tumor cells and was strong in squamous cell carcinomas, but only weak in adenocarcinomas (2.6+/-0.5 vs. 1.2+/-0.4, respectively; P<0.005). In accordance, argpyrimidine was found in the human lung squamous carcinoma cell line SW1573, while it was almost absent in the adenocarcinoma cell line H460. Heat shock protein 27 (Hsp27) was identified as a major argpyrimidine-modified protein. In agreement with a previously described anti-apoptotic activity of argpyrimidine-modified Hsp27, the percentage of active caspase-3 positive tumor cells in squamous cell carcinomas was significantly lower when compared to adenocarcinomas. In addition, incubation with cisplatin induced almost no caspase-3 activation in SW1573 cells while a strong activation was seen in H460 cells; which was significantly reduced by incubation with an inhibitor of glyoxalase I, the enzyme that catalyzes the conversion of methylglyoxal. These findings suggest that a high level of argpyrimidine-modified Hsp27 is a mechanism of cancer cells for evasion of apoptosis

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly - A prospective randomized study in squamous cell head and neck cancer

BACKGROUND. The main objective of this study was to investigate whether non-daily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer. METHODS. Ninety-one patients who received bilateral irradiation for head and neck cancer were included. Thirty patients received no armfostine (AMI-0), 31 patients received amifostine at a dose of 200 mg/m(2) 3 times weekly (AMI-3), and 30 patients received amifostine at a dose of 200 mg/m(2) daily (5 times weekly) (AMI-5). Acute and late xerostomia and quality of life (QOL) were assessed at baseline, 6 weeks later, and at 6-month intervals from 6 months to 24 months postradiotherapy. RESULTS. Grade 2 or greater late xerostomia differed significantly at 6 months (AMI-0 74% vs. AMI-3 67% vs. AMI-5 52%; P = .03), but not thereafter. During follow-up, patient-rated xerostomia deteriorated more in AMI-0 patients (mean difference score:, 52 for AMI-0 compared with 25 for AMI-3, and 29 for AMI-5; P = .01). Nausea and emesis were reported most frequently as side effect, but Grade 2 or greater toxicity was observed in only 4 patients. However, 28% of patients discontinued amifostine before the end of radiotherapy. CONCLUSIONS. Long-term, patient-rated xerostomia was less for the AMI-3 and AMI-5 groups through 2-year follow-up, but no difference was noted between the AMI-3 and AMI-5 groups. For late xerostomia according to the Radiation Therapy Oncology Group criteria, the same effect was observed at 6 months, but not thereafter