Search PubMed⌕ Search

Biomedical subjects

Lei Dong

Publications and source records attributed to Lei Dong.

At least 37 records · Page 2Linked to original sources

[Preparation of tetrandrine solid lipid nanoparticles].

OBJECTIVE: To prepare solid lipid nanoparticles (SLN) loaded tetrandrine (TET) extracted from traditional Chinese medicine with ultrasonication and high pressure homogenization, and to compare the physicochemical characteristics of the particles produced by the two methods. METHODS: TET was incorporated into SLN by ultrasonication and high pressure homogenization separately. Transmission electron microscopy was employed to study the shape. Particle characterization system and Zeta potential analyzer were used to study the diameter and Zeta potential of SLN in suspension. The entrapment efficiency was determined with the high-performance liquid chromatography. The stability of SLN was also studied. RESULTS: TET-SLNs prepared by these two methods were sheet-shaped and irregular, but the SLNs prepared by high pressure homogenization were smaller. The mean diameter of SLN prepared by ultrasonication was (92 +/- 6) nm with Zeta potential of (-21.11 +/- 2.12) mV in distilled water, and the mean entrapment efficiency was 95.27%. The mean diameter of TET-SLN prepared by high pressure homogenization was (47 +/- 3) nm with Zeta potential of (-32.99 +/- 2.54) mV, and up to 97.82% of TET was incorporated. The diameter of SLN prepared by high pressure homogenization and ultrasonication were (52 +/- 5) nm and (168 +/- 12) nm after 90 days of storage at room temperature. CONCLUSION: Compared with ultrasonication, high pressure homogenization is a better method to prepare TET-SLN, which is smaller, steadier and highly incorporated.

Alkaloids↗

Effectiveness of noncoplanar IMRT planning using a parallelized multiresolution beam angle optimization method for paranasal sinus carcinoma.

PURPOSE: To determine the effectiveness of noncoplanar beam configurations and the benefit of plans using fewer but optimally placed beams designed by a parallelized multiple-resolution beam angle optimization (PMBAO) approach. METHODS AND MATERIALS: The PMBAO approach uses a combination of coplanar and noncoplanar beam configurations for intensity-modulated radiation therapy (IMRT) treatment planning of paranasal sinus cancers. A smaller number of beams (e.g. 3) are first used to explore the solution space to determine the best and worst beam directions. The results of this exploration are then used as a starting point for determining an optimum beam orientation configuration with more beams (e.g. 5). This process is parallelized using a message passing interface, which greatly reduces the overall computation time for routine clinical practice. To test this approach, treatment for 10 patients with paranasal sinus cancer was planned using a total of 5 beams from a pool of 46 possible beam angles. The PMBAO treatment plans were also compared with IMRT plans designed using 9 equally spaced coplanar beams, which is the standard approach in our clinic. Plans with these two different beam configurations were compared with respect to dose conformity, dose heterogeneity, dose-volume histograms, and doses to organs at risk (i.e., eyes, optic nerve, optic chiasm, and brain). RESULTS: The noncoplanar beam configuration was superior in most paranasal sinus carcinoma cases. The target dose homogeneity was better using a PMBAO 5-beam configuration. However, the dose conformity using PMBAO was not improved and was case dependent. Compared with the 9-beam configuration, the PMBAO configuration significantly reduced the mean dose to the eyes and optic nerves and the maximum dose to the contralateral optical path (e.g. the contralateral eye and optic nerve). The maximum dose to the ipsilateral eye and optic nerve was also lower using the PMBAO configuration than using the 9-beam configuration, although this difference was not significant. The mean doses to the optic chiasm and brain are marginally lower using the PMBAO configuration than using 9-beam configuration. The maximum doses to the optic chiasm and brain are the same with the PMBAO configuration and the 9-beam configuration. CONCLUSION: Parallelized multiple-resolution beam angle optimization with an optimized noncoplanar beam configuration is an effective and practical approach for IMRT treatment planning. Five-beam treatment plans optimized using the PMBAO are at least equivalent to, and overall better than, the plans using 9 equally spaced coplanar beams.

Humans↗

Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats.

AIM: To investigate the effects of entero-hepatic bile acid circulation on the inter-digestive migrating myoelectrical complex (MMC) in rats. METHODS: Thirty-two rats were divided into four groups. Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of them were ligated around the upper part of common bile duct (CBD). The experiments were performed in conscious and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid (UDCA) and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed. RESULTS: A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared. increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase II-like activity and decreased duration of phase I and III activity. Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase III of duodenal origin compared to the normal group. CONCLUSION: Entero-hepatic bile acid circulation initiates inter-digestive MMC of duodenal origin.

Animals↗

Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy.

PURPOSE: To retrospectively test the hypothesis that rectal distension on the planning computed tomography (CT) scan is associated with an increased risk of biochemical and local failure among patients irradiated for prostate carcinoma when a daily repositioning technique based on direct prostate-organ localization is not used. METHODS AND MATERIALS: This study included 127 patients who received definitive three-dimensional conformal radiotherapy for prostate cancer to a total dose of 78 Gy at The University of Texas M. D. Anderson Cancer Center. Rectal distension was assessed by calculation of the average cross-sectional rectal area (CSA; defined as the rectal volume divided by length) and measuring three rectal diameters on the planning CT. The impact of rectal distension on biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or greater late rectal bleeding was assessed. RESULTS: The incidence of biochemical failure was significantly higher among patients with distended rectums (CSA >11.2 cm(2)) on the planning CT scan (p = 0.0009, log-rank test). Multivariate analysis indicates that rectal distension and high-risk disease are independent risk factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to 9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The probability of residual tumor without evidence of radiation treatment (as scored by the pathologist) increased significantly with rectal distension (p = 0.010, logistic analysis), and a lower incidence of Grade 2 or greater late rectal bleeding within 2 years was simultaneously observed with higher CSA values (p = 0.031, logistic analysis). CONCLUSIONS: We found strong evidence that rectal distension on the treatment-planning CT scan decreased the probability of biochemical control, local control, and rectal toxicity in patients who were treated without daily image-guided prostate localization, presumably because of geographic misses. Therefore, an empty rectum is warranted at the time of simulation. These results also emphasize the need for image-guided radiotherapy to improve local control in irradiating prostate cancer.

Aged↗

Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs.

AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoelectric complex (MMC) in guinea pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime. RESULTS: After cholecystectomy, there were parallel falls in duration of phase I, II, III and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant. CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postcholecystectomy syndrome.

Animals↗

Expression of gamma-aminobutyric acid A receptor subunits alpha1, beta1, gamma2 mRNA in rats with hepatic encephalopathy.

AIM: To investigate the mRNA expression of gamma-aminobutyric acid A (GABA(A)) receptor subunits alpha(1), beta(1), gamma(2) in different parts of the brain of rats with hepatic encephalopathy. METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into two groups: (1) hepatic encephalopathy model group (n = 6), which was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg/kg) for three consecutive days; (2) control group (n = 6), in which the rats were treated with same dose of normal saline solution. After the freeze slice of cerebrum was made, in situ hybridization was used to detect the mRNA of GABAA receptor subunits alpha(1), beta(1), and gamma(2) in rat cerebral cortex, basal nuclei, substantia nigra and hippocampi. Image data were collected and analyzed quantitatively by QWin550CW model image signal gather and analysis system. RESULTS: In rats with hepatic encephalopathy, mRNA expression levels of GABA(A) receptor subunits alpha(1), beta(1) increased significantly in basal nuclei, substantia nigra pars compacta, substantia nigra pars reticularis and hippocampi (144.7+/-15.67/184.14+/-4.41, 60.61+/-33.66/113.07+/-32.44, 87.71+/- 21.25/128.40+/-18.85, 122.34+/-5.56/161.60+/-4.56, 123.29+/-5.21/140.65+/-4.15, 123.40+/-4.42/140.09+/-4.52, 124.76+/-4.18/140.09+/-4.12, 141.62+/-15.09/182.80 +/-5.20, 69.13+/-30.74/134.21+/-43.76, 87.87+/-25.16/151.01+/-19.49, 122.14+/-6.30 /162.33+/-3.92, 122.81+/-5.09/137.19+/-7.12, 123.00+/-4.63/138.11+/-5.92, 125.75 +/-2.43/138.81+/-6.10, P<0.01), but did not change in the cerebral cortex compared to the control group. Similar changes were found in the mRNA expression levels of GABA(A) receptor subunit gamma(2), which increased significantly in basal nuclei, substantia nigra pars compacta, substantia nigra pars reticularis (136.81+/-26.41/167.97+/-16.23, 51.00+/-36.14/113.18+/-36.52, 86.35+/-20.30/ 126.90+/-19.74, P<0.01), CA1 of hippocampal (162.15+/-9.05/178.62+/-6.45, P<0.05), and no changes were found in the cerebral cortex and CA2, CA3, CA4 of hippocampi. CONCLUSION: In rats with hepatic encephalopathy, mRNA expression levels of GABA(A) receptor subunits alpha(1), beta(1), gamma(2) increase significantly in basal nuclei, substantia nigra and hippocampi, suggesting that the changes of mRNA expression levels in GABA(A) receptor subunits may contribute to the pathogenesis of hepatic encephalopathy.

Animals↗

Validation of an accelerated 'demons' algorithm for deformable image registration in radiation therapy.

A greyscale-based fully automatic deformable image registration algorithm, originally known as the 'demons' algorithm, was implemented for CT image-guided radiotherapy. We accelerated the algorithm by introducing an 'active force' along with an adaptive force strength adjustment during the iterative process. These improvements led to a 40% speed improvement over the original algorithm and a high tolerance of large organ deformations. We used three methods to evaluate the accuracy of the algorithm. First, we created a set of mathematical transformations for a series of patient's CT images. This provides a 'ground truth' solution for quantitatively validating the deformable image registration algorithm. Second, we used a physically deformable pelvic phantom, which can measure deformed objects under different conditions. The results of these two tests allowed us to quantify the accuracy of the deformable registration. Validation results showed that more than 96% of the voxels were within 2 mm of their intended shifts for a prostate and a head-and-neck patient case. The mean errors and standard deviations were 0.5 mm+/-1.5 mm and 0.2 mm+/-0.6 mm, respectively. Using the deformable pelvis phantom, the result showed a tracking accuracy of better than 1.5 mm for 23 seeds implanted in a phantom prostate that was deformed by inflation of a rectal balloon. Third, physician-drawn contours outlining the tumour volumes and certain anatomical structures in the original CT images were deformed along with the CT images acquired during subsequent treatments or during a different respiratory phase for a lung cancer case. Visual inspection of the positions and shapes of these deformed contours agreed well with human judgment. Together, these results suggest that the accelerated demons algorithm has significant potential for delineating and tracking doses in targets and critical structures during CT-guided radiotherapy.

Algorithms↗

An automatic CT-guided adaptive radiation therapy technique by online modification of multileaf collimator leaf positions for prostate cancer.

PURPOSE: To propose and evaluate online adaptive radiation therapy (ART) using in-room computed tomography (CT) imaging that detects changes in the target position and shape of the prostate and seminal vesicles (SVs) and then automatically modifies the multileaf collimator (MLC) leaf pairs in a slice-by-slice fashion. METHODS AND MATERIALS: For intensity-modulated radiation therapy (IMRT) using a coplanar beam arrangement, each MLC leaf pair projects onto a specific anatomic slice. The proposed strategy assumes that shape deformation is a function of only the superior-inferior (SI) position. That is, there is no shape change within a CT slice, but each slice can be displaced in the anteroposterior (AP) or right-left (RL) direction relative to adjacent slices. First, global shifts (in SI, AP, and RL directions) were calculated by three-dimensional (3D) registration of the bulk of the prostate in the treatment planning CT images with the daily CT images taken immediately before treatment. Local shifts in the AP direction were then found using slice-by-slice registration, in which the CT slices were individually registered. The translational shift within a slice could then be projected to a translational shift in the position of the corresponding MLC leaf pair for each treatment segment for each gantry angle. Global shifts in the SI direction were accounted for by moving the open portal superiorly or inferiorly by an integral number of leaf pairs. The proposed slice-by-slice registration technique was tested by using daily CT images from 46 CT image sets (23 each from 2 patients) taken before the standard delivery of IMRT for prostate cancer. A dosimetric evaluation was carried out by using an 8-field IMRT plan. RESULTS: The shifts and shape change of the prostate and SVs could be separated into 3D global shifts in the RL, AP, and SI directions, plus local shifts in the AP direction, which were different for each CT slice. The MLC leaf positions were successfully modified to compensate for these global shifts and local shape variations. The ART method improved geometric coverage of the prostate and SVs compared with the couch-shift method, particularly for the superior part of the prostate and all the SVs, for which the interfraction shape change was the largest. The dosimetric comparison showed that the ART method covered the target better and reduced the rectal dose more than a simple couch-translation method. CONCLUSIONS: ART corrected for interfraction changes in the position and shape of the prostate and SVs and gave dose distributions that were considerably closer to the planned dose distributions than could be achieved with simple alignment strategies that neglect shape change. The ART proposed in this investigation requires neither contouring of the daily CT images nor extensive calculations; therefore, it may prove to be an effective and clinically practical solution to the problem of interfraction shape changes.

Algorithms↗

Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy.

PURPOSE: In this era of dose escalation, the benefit of higher radiation doses for low-risk prostate cancer remains controversial. For intermediate-risk patients, the data suggest a benefit from higher doses. However, the quantitative characterization of the benefit for these patients is scarce. We investigated the radiation dose-response relation of tumor control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. We also investigated the differences in the dose-response characteristics using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition vs. an alternative biochemical failure definition. METHODS AND MATERIALS: This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment between 1987 and 1998. The low-risk patients had 1992 American Joint Committee on Cancer Stage T2a or less disease as determined by digital rectal examination, prostate-specific antigen (PSA) levels of < or =10 ng/mL, and biopsy Gleason scores of < or =6. The intermediate-risk patients had one or more of the following: Stage T2b-c, PSA level of < or =20 ng/mL but >10 ng/mL, and/or Gleason score of 7, without any of the following high-risk features: Stage T3 or greater, PSA >20 ng/mL, or Gleason score > or =8. The logistic models were fitted to the data at varying points after treatment, and the dose-response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises, with the time to failure backdated to the mid-point between the nadir and the first rise. The second biochemical failure definition used was a PSA rise of > or =2 ng/mL above the current PSA nadir (CN + 2). The failure date was defined as the time at which the event occurred. Local, nodal, and distant relapses and the use of salvage hormonal therapy were also failures. RESULTS: On the basis of the ASTRO definition, at 5 years after radiotherapy, the dose required for 50% tumor control (TCD(50)) for low-risk patients was 57.3 Gy (95% confidence interval [CI], 47.6-67.0). The gamma50 was 1.4 (95% CI, -0.1 to 2.9) around 57 Gy. A statistically significant dose-response relation was found using the ASTRO definition. However, no dose-response relation was noted using the CN + 2 definition for these low-risk patients. For the intermediate-risk patients, using the ASTRO definition, the TCD(50) was 67.5 Gy (95% CI, 65.5-69.5) Gy and the gamma50 was 2.2 (95% CI, 1.1-3.2) around TCD(50). Using the CN + 2 definition, the TCD(50) was 57.8 Gy (95% CI, 49.8-65.9) and the gamma50 was 1.4 (95% CI, 0.2-2.5). Recursive partitioning analysis identified two subgroups within the low-risk group, as well as the intermediate-risk group: PSA level <7.5 vs. > or =7.5 ng/mL. Most of the benefit from the higher doses for the low- and intermediate-risk group was derived from the patients with the higher PSA values. For the low-risk group, the dose-response curves essentially plateaued at 78 Gy. CONCLUSION: A dose-response relation was found using the ASTRO definition for low-risk prostate cancer. However, we found only marginal or no dose-response relation when the CN + 2 definition was used. Most of the benefit from the higher doses derived from low-risk patients with higher PSA levels. In all cases, little projected gain appears to exist at doses >78 Gy for these patients. A dose-response relation was noted for the intermediate-risk patients using either the CN + 2 or ASTRO definition. Most of the benefit from the higher doses also derived from the intermediate-risk patients with higher PSA levels. Some room for improvement appears to exist with additional dose increases in this group.

Aged↗

Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes.

PURPOSE: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. METHODS AND MATERIALS: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye-view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose-volume histograms and dose-volume and dose-response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today's image, and (c) from a new full-fledged IMRT plan designed based on today's image. RESULTS: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye-view are a good approximation of full-fledged replanning compared with other alternatives. CONCLUSIONS: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.

Algorithms↗

Implementation and validation of a three-dimensional deformable registration algorithm for targeted prostate cancer radiotherapy.

PURPOSE: Daily prostate deformation hinders accurate calculation of dose, especially to intraprostatic targets. We implemented a three-dimensional deformable registration algorithm to aid dose tracking for targeted prostate radiotherapy. METHODS AND MATERIALS: The algorithm registers two computed tomography (CT) scans by iteratively minimizing their differences in image intensity. For validation, we measured the accuracy in registering (a) a pelvic CT set to its mathematically deformed counterpart, (b) CT scans of a deformable pelvic phantom with and without an endorectal balloon inflated, to simulate intraprostatic targets, 23 CT-opaque seeds were embedded in the prostate, and (c) two pelvic CT scans of a patient obtained on 2 separate days. RESULTS: The mean (SD) error in registering the pelvic CT set to its transformed set was 0.5 mm (1.5), with correlation coefficient improvement from 0.626 to 0.991. Using the deformable pelvic phantom, the correlation coefficient improved from 0.543 to 0.816 after registration. The mean (SD) error in tracking the intraprostatic seeds was 0.8 mm (0.5). The correlation coefficient improved from 0.610 to 0.944 after registration of the two patient CT sets. CONCLUSION: The algorithm had an accuracy of about 1 mm. It could be used for optimizing dose calculation and delivery for prostate radiotherapy.

Algorithms↗

Assessing the impact of an alternative biochemical failure definition on radiation dose response for high-risk prostate cancer treated with external beam radiotherapy.

PURPOSE: The American Society for Therapeutic Radiology and Oncology (ASTRO) biochemical failure definition has recently been compared with various alternative definitions. We assessed the effect of using an alternative failure definition on the dose-response characteristics of high-risk prostate cancer treated with radiotherapy alone. METHODS AND MATERIALS: This study included 363 high-risk prostate cancer patients treated with external beam radiotherapy alone from 1987 to 1999. These patients have one or more of the following: 1992 American Joint Committee on Cancer (AJCC) digital rectal examination (DRE) stage > or = cT3, prostate-specific antigen (PSA) > 20 ng/mL, and/or biopsy Gleason score > or = 8. We previously reported the dose response based on the ASTRO definition for these patients. In this study, a biochemical failure is defined as a PSA rise > or = 2 ng/mL above the current nadir PSA (CN + 2). The failure date is defined as the time at which the event occurred (i.e., the call date). RESULTS: Using CN + 2, the tumor control probability (TCP) continues to decrease with time as opposed to reaching a plateau as with the ASTRO definition. At 5 years, TCD50 (95% CI), the dose to achieve 50% tumor control, for high-risk prostate cancer, is 70.4 (68.0-72.9) Gy using CN + 2 [ASTRO: 75.5 (70.7-80.2) Gy]. The relative slope, gamma50 (95% CI) is 1.8 (0.8-2.8) [ASTRO: 1.7 (0.7-2.7)]. Recursive partitioning again identified two subgroups: PSA < vs. > or = 13 ng/mL (ASTRO: PSA < or = vs. > 20 ng/mL). The difference in TCD50 between the two subgroups is about 20 Gy at 5 years (ASTRO: about 15 Gy at 5 years). CONCLUSION: This analysis using the CN + 2 failure definition continues to show a dose response for the high-risk group of patients. However, the dose-response characteristics differ from those estimated using the ASTRO definition. We observed that the position (TCD50) and steepness (gamma50) of the dose-response curve changed with time as long as the TCP continued to decrease. This suggests that the dose response characteristics derived from data with longer follow-up may be different from those derived with shorter follow-up using the CN + 2 or similar failure definitions which do not back-date the failure. These changes in dose-response characteristics as well as the time dependence of dose response should be noted when investigators design dose escalation trials for the high-risk prostate cancer patients.

Adenocarcinoma↗

Present status of serum lipid levels in Beijing professional populations and its trend of changes over 15 years--a collaborative study of seven research and clinical laboratories in Beijing.

BACKGROUND: China's economy has been growing rapidly since 1980, which may have affected blood lipid levels. We carried out a study on serum lipid levels and prevalence of lipid abnormalities in Beijing professional populations in 2001-2002 and assessed the changing trends of lipid levels by comparing the results with that of a similar study in 1984-1986. METHODS: The study population included 31,068 government employees, medical and educational workers and scientific research personnel (male/female 6:4). All participants had physical examination and blood chemistry tests. Lipid parameters analyzed included total cholesterol, low- and high-density lipoprotein (LDL and HDL) cholesterol and triglyceride. RESULTS: Total cholesterol, LDL cholesterol and triglyceride concentrations increased significantly as compared with the 1984-1986 study, but the variations of lipid levels with age and sex remained unchanged. Age-adjusted prevalence of dyslipidemia and its distribution in different sexes and age groups were statistically analyzed. Comparing the results with the data of the US in the 1990s, total cholesterol concentration was lower by 16 mg/dl in men and 18 mg/dl in women, whereas LDL cholesterol concentration was lower by 20 mg/dl in men and 15 mg/dl in women. HDL cholesterol was significantly higher than the US in both genders. CONCLUSIONS: The mean levels of total cholesterol (LDL cholesterol ) increased rapidly in the 1980s, stabilized and descended slightly in 1990s. Coronary lipid risk level in Beijing professional populations is significantly lower than in the US.

Administrative Personnel↗

Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector.

Delivery of oligonucleotide to specific cells and maintenance of its biological function are important for nucleic acid therapy. The objective of this paper is to demonstrate that galactosylated low molecular weight chitosan (gal-LMWC) is a safe and effective vector of antisense oligonucleotide (ASO) and plasmid DNA for the hepatocyte targeting delivery. Gal-LMWC has been successfully prepared and MTT cytotoxic assay shows that cytotoxicity of gal-LMWC is lower than that of high molecular weight chitosan (HMWC) and low molecular weight chitosan (LMWC) in HepG2 cells. Using a complex coacervation process, gal-LMWC can form stable nano-complexes with plasmid DNA or with ASO by the electrostatic interaction. The morphometrics, particle size, and the zeta potential of gal-LMWC/ASO complexes and gal-LMWC/plasmid DNA complexes are very similar. The transfection efficiency by using gal-LMWC vector is significantly higher than that of naked DNA or naked ASO in HepG2 cells. Transfection efficiency of gal-LMWC/ASO complexes and gal-LMWC/plasmid DNA complexes depends on the molar ratio of the positive chitosan amino group and the negative DNA phosphate group (N/P ratio) strongly. Inhibition experiments confirm that the enhanced transfection efficiency is due to the ASGR mediated endocytosis of the gal-LMWC/ASO complexes or gal-LMWC/DNA complexes. These results suggest that gal-LMWC can be used in gene therapy to improve the transfection efficiency in vitro and in vivo.

Cell Line, Tumor↗

Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.

The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Loktrade mark bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2x2-cm field size. The dose beyond the interface recovered quickly and the dose reductions due to air cavity were 50%, 28%, 11%, and 1% at 2, 5, 10, and 15 mm, respectively, from the distal air-tissue interface. Evaluating the dose profiles of the more clinically relevant situation revealed the dose at air-tissue interface was approximately 15% lower in comparison to that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, there was only an 8% and 5% differential, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal with or without the air cavity. The median follow-up was 31.3 months. Rectal toxicity profile was very favorable: 81% (94/116) patients had no rectal complaint while 10.3% (12/116), 6.9% (8/116), and 1.7% (2/116) had grade 1, 2, and 3 toxicity, respectively. There was no grade 4 rectal toxicity. DVH analysis revealed that none of the patients had more than 25% of the rectum receiving 70 Gy or greater. Rectal balloon has rendered anterior rectal wall sparing by its dosimetric effects. In addition, it has reduced rectal volume, especially posterior and lateral rectal wall receiving high-dose radiation by rectal wall distension. Both factors may have contributed to decreased rectal toxicity achieved by IMRT despite dose escalation and higher than conventional fraction size. The findings have clinical significance for future very high-dose escalation trials whereby radiation proctitis is a major limiting factor.

Catheterization↗

Ultrasound-based localization.

Ultrasound is a noninvasive, relatively easy, rapid, and real-time imaging technique for organ targeting for radiotherapy. Its application has been developed to a greater extent in prostate cancer than in other sites in which it has been shown to improve the accuracy of daily treatment delivery. With the move toward dose escalation and the need to maximally spare the adjacent critical structures through more conformal therapy and smaller field margins, an innovative technique for accurate and reproducible tumor targeting is mandatory. Basic ultrasound principles and organ location lend themselves well to the application of this modality in prostate cancer. Promising results using daily ultrasound-guided B-mode acquisition and targeting for patients with upper abdominal tumors suggest an area for additional trials and study. For breast cancer radiotherapy, ultrasound serves to define involved primary and nodal sites, especially in patients in whom surgical evaluation will not be the first therapeutic step.

Abdominal Neoplasms↗

Elastic image mapping for 4-D dose estimation in thoracic radiotherapy.

PURPOSE: Demonstrate the path integration of a four-dimensional (4-D) dose distribution onto the 3-D anatomy. MATERIALS AND METHODS: A computer-generated 4-D thoracic phantom with a lung tumour was constructed. Eight respiratory phases were generated. A radiotherapy treatment plan was applied to all the phases resulting in a 4-D dose distribution. An elastic image registration algorithm was used to find the vector displacement between all the image elements and the end expiration phase. The path-integrated tissue dose distribution and each component dose distribution were compared with the planned dose distribution. RESULTS: Numerical path integration was performed to calculate the tissue dose distribution. Loss of tumour coverage was the predominant effect observed with tumour motion in this study. The loss was asymmetric and dependent on the tumour trajectory. CONCLUSION: The elastic image registration allowed an accurate path integration through a 4-D data set to produce an accurate 3-D tissue dose estimate.

Artifacts↗