1,721,197 research outputs found
Flow cytometric measurement of proliferating cell nuclear antigen (PCNA) in solid tumors
No full textPurpose: The importance of cell kinetic parameters for prognosis and therapeutic strategy is widely accepted in oncology. Repopulation is a major problem in radiotherapy of head and neck tumors. Various assays exist for measuring the proliferation characteristics of individual tumors. However, the existing methods have several drawbacks. Materials and Methods: PCNA (proliferating cell nuclear antigen) is expressed in a cell cycle dependent manner. There is a DNA-bound, S-phase specific fraction and a nucleoplasmatic, extractable fraction, which is detectable in all phases except G0. We describe a method for simultaneous measurement of PCNA and DNA in solid tumors using flow cytometry. The assay was applied to three different sublines (AT1, HI, H) of the Dunning rat prostate tumor R3327 and biopsies of twelve human head and neck squamous cell carcinomas. The PCNA-assay was compared to the standard BrdUrd-assay (bromodeoxyuridine) by simultaneous measurement of PCNA and BrdUrd in the animal tumors. Results: Percentages of PCNA-positive cells of 29 ± 4% (AT1), 25 ± 7% (HI) and 3 ± 1% (H) were calculated for the animal tumors with good rank correlation with the BrdUrd-LI. The PCNA-indices for human tumors ranged from 5 ± 1% up to 70 ± 9%. Conclusion: The flow cytometric PCNA-assay can be applied to standard biopsy material and yields reproducible results with an intratumor variation of about 5% which is small compared to the wide range of PCNA-indices in our series. The method may enhance the pretherapeutic assessment of tumor proliferation kinetics
Robustness of sweeping-window arc therapy treatment sequences against intrafractional tumor motion
Full text linkPurpose: Due to the potentially periodic collimator dynamic in volumetric modulated arc therapy (VMAT) dose deliveries with the sweeping-window arc therapy (SWAT) technique, additional manifestations of dosimetric deviations in the presence of intrafractional motion may occur. With a fast multileaf collimator (MLC), and a flattening filter free dose delivery, treatment times close to 60 s per fraction are clinical reality. For these treatment sequences, the human breathing period can be close to the collimator sweeping period. Compared to a random arrangement of the segments, this will cause a further degradation of the dose homogeneity. Methods: Fifty VMAT sequences of potentially moving target volumes were delivered on a two dimensional ionization chamber array. In order to detect interplay effects along all three coordinate axes, time resolved measurements were performed twice-with the detector aligned in vertical (V) or horizontal (H) orientation. All dose matrices were then moved within a simulation software by a time-dependent motion vector. The minimum relative equivalent uniform dose EUDr,m for all breathing starting phases was determined for each amplitude and period. Furthermore, an estimation of periods with minimum EUD was performed. Additionally, LINAC logfiles were recorded during plan delivery. The MLC, jaw, gantry angle, and monitor unit settings were continuously saved and used to calculate the correlation coefficient between the target motion and the dose weighed collimator motion component for each direction (CC, LR, AP) separately. Results: The resulting EUDr,m were EUDr,m(CCV) = (98.3 +/- 0.6)%, EUDr,m(CCH) = (98.6 +/- 0.5)%, EUDr,m(AP(V)) = (97.7 +/- 0.9)%, and EUDr,m(LRH) = (97.8 +/- 0.9)%. The overall minimum relative EUD observed for 360. arc midventilation treatments was 94.6%. The treatment plan with the shortest period and a minimum relative EUD of less than 97% was found at T = 6.1 s. For a partial 120 degrees arc, an EUDr,m = 92.0% was found. In all cases, a correlation coefficient above 0.5 corresponded to a minimum in EUD. Conclusions: With the advent of fast VMAT delivery techniques, nonrobust treatment sequences for human breathing patterns can be generated. These sequences are characterized by a large correlation coefficient between a target motion component and the corresponding collimator dynamic. By iteratively decreasing the maximum allowed dose rate, a low correlation coefficient and consequentially a robust treatment sequence are ensured. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License
IMRT FOR GASTRIC CANCER: WHAT IS ITS FULL POTENTIAL? IN REGARD TO ALANI ET AL. (INT J RADIAT ONCOL BIOL PHYS 2009;74:562-566)
No full textIntensity modulated radiosurgery of brain metastases with flattening filter-free beams
No full textPurpose: Flattening filter free (FFF) irradiation potentially reduces treatment delivery time in radiosurgery thus eliminating intrafraction motion and increasing patient comfort. We compared plan quality and efficiency of VMAT and IMRT plans for FFF- and standard delivery for brain metastases with single fraction doses of 20 Gy and validated the dosimetric accuracy of the FFF delivery. Material and Methods: CT data of 15 patients with brain metastases were included in this study. For every patient, 2 IMRT- and 2 VMAT-plans were created using a high-resolution MLC with two different delivery modes (6 MV standard vs. 6 MV FFF). Plan quality and efficiency was assessed by analysis of conformity, homogeneity, dose gradients, treatment delivery time and number of monitor units (MU). Dosimetric evaluation was performed for 10 FFF plans with radiochromic film and ion chamber. Results: Plan quality was similar for both approaches. FFF provided a mean treatment time reduction of 51.5% with similar MU for VMAT and IMRT for this low-modulation paradigm. The dosimetric validations showed an absolute dose deviation of +0.93 +/- 0.99% and gamma-index analysis (3%/3 mm and 3%/1 mm) resulted in agreement of 99.08 +/- 1.58% respectively 93.46 +/- 2.41%. Conclusion: FFF radiosurgery is an efficient technique for intensity modulated hypofractionated or single fraction treatments with similar plan quality when compared to flattened beams at reduced treatment time. (C) 2013 Elsevier Ireland Ltd. All rights reserved
Should patients with locally advanced, non-metastatic carcinoma of the pancreas be irradiated?
No full textA small number of patients exist with carcinoma of the pancreas with an inoperable but not metastasized tumor. Prospective randomized studies defined the standard of combined radiochemotherapy during the early 1980s for these patients. Since then, new drugs have shown considerable activity and in parallel improvements in radiotherapy treatment planning and delivery have been achieved. Therefore, it is time to ask whether patients with locally advanced, inoperable pancreatic cancer without metastases should still be irradiated or not. This review summarizes the current literature on combined radiochemotherapy for locally advanced carcinoma of the pancreas. Median survival times of 10-11 months and 1-year survival rates of about 40% can be achieved with modern radiochemotherapy regimens. Copyright (C) 2003 S. Karger AG, Basel and IAP
COMPARISON OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) STAINING AND BRDURD-LABELING INDEX UNDER DIFFERENT PROLIFERATIVE CONDITIONS IN-VITRO BY FLOW-CYTOMETRY
Full text linkPC10 is a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The staining pattern in immunochemistry depends on fixation and detergent extraction treatment. The aim of this study was to validate the flow cytometric PCNA assay against Bromodeoxyuridine-labelling index (BrdUrd-LI) under different proliferative conditions in vitro. Expression of PCNA in methanol fixed cells with, and without, prior detergent extraction with EDTA/Triton was compared to BrdUrd-labelling index in NIH-3T3 fibroblasts and human Caski tumour cells in exponential phase and under confluent conditions. Serum stimulation and serum starvation conditions were studied. The results for BrdUrd-LI and PCNA-index after extraction showed good correlation for 3T3 fibroblasts and for Caski cells, with some differences for serum withdrawn Caski cells. There was no correlation between the number of cells that were positive for PCNA without extraction and BrdUrd-LI. Spheroid cells with G(1)-DNA-content showed an almost synchronous recruitment and progression through the cell cycle after trypsination and replating. Tightly bound PCNA paralleled this synchronicity whereas total PCNA did not change significantly. The results demonstrate that immunochemical detection of non-extractable PCNA-index gives similar results as compared with BrdUrd-labelling index under different proliferative conditions in vitro for different monolayer cell lines, whereas without extraction PCNA does not correlate with BrdUrd-LI in these fast growing cell lines due to its long half-life. PCNA expression parallels the progression through the cell cycle in V79 spheroids, a primitive model of tumour growth
Inhibition of 13-cis retinoic acid-induced gene expression of homeobox B7 by thalidomide
No full textThalidomide and 13-cis retinoic acid (RA) show anticancer effects as sole agents or in combination with other drugs. However, induction of homeobox (HOX) gene expression by 13-cis RA may contribute to tumor progression thereby potentially limiting its efficacy. The purpose was to test if thalidomide can inhibit 13-cis RA-induced HOXB7 expression and whether thalidomide may enhance the antiproliferative effect of 13-cis RA in U343MG glioblastoma cells. Quantitative real-time PCR showed significant inhibition of 13-cis RA-induced HOXB7 expression by thalidomide with IC50 ∼ 0.1-0.2 μg/ml when given simultaneously with 13-cis RA but not when administered 18h later (p < 0.0001). 13-cis RA alone inhibited proliferation and colony formation in a concentration-dependent manner whereas growth inhibition by thalidomide alone at 5-100 μg/ml was constant at 80-90% of controls. At 10% serum concentration, growth inhibition by a combination of the 2 drugs was additive but at 1% serum, growth inhibition was synergistic. It is concluded that thalidomide inhibits the RA-induced HOXB7 expression in glioblastoma cells and that 13-cis RA/thalidomide combinations can in principle enhance cytotoxicity. The improved cell kill induced by thalidomide is attributed to down-regulation of growth stimulatory factors induced by 13-cis RA. Implications for the modus operandi of thalidomide in embryogenesis are noted. © 2007 Wiley-Liss, Inc
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