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Purpose: To assess the feasibility of treating lung SBRT patients with the ipsilateral arm adducted beside the body instead of elevated above the head. Methods: Patients receiving lung SBRT at our institution are typically treated with both arms raised above their head. However, several patients had difficulty maintaining their arms in an elevated position. In this study, lung SBRT patients who underwent PET-CT imaging with an adducted ipsilateral arm were selected to investigate the dosimetric effects of this treatment setup. PET-CT datasets were fused with treatment planning CT images to simulate the adducted arm position. One VMAT treatment plan was created per patient using the Pinnacle treatment planning system. Plans were optimized to achieve minimal dose to the ipsilateral arm while keeping the target coverage and critical structure doses within clinical limits. The target dose coverage, conformity index (CI) for the target, and DVHs of critical structures for the adducted arm plan were calculated. These parameters were compared with the clinical plan and reported along with the mean and maximum doses of the ipsilateral arm. Results: The target coverage, CI and DVHs for the adducted arm plans of two patients (one with peripheral lesion and one with central lesion) were comparable with the clinical plans. Dose constraints for the chest wall limited further reduction of ipsilateral arm doses for the peripheral lesion plan. The mean ipsilateral arm doses for the central and peripheral lesions were 0.33 Gy and 2.4 Gy, respectively. The maximum ipsilateral arm doses for the central and peripheral lesions were 1.0 Gy and 6.2 Gy, respectively. Conclusion: The results suggested patients with central lung SBRT tumors were more suitable for treatment with the adducted arm position. More patients with various lung tumor locations will be studied to find optimal tumor locations for treatment with this arm position.

Purpose: To correlate in vitro cell kill with linear energy transfer (LET) spectra using Monte Carlo simulations and knowledge obtained from previous high-throughput in vitro proton relative biological effectiveness (RBE) measurements. Methods: The Monte Carlo simulation toolkit Geant4 was used to design the experimental setups and perform the dose, dose-averaged LET, and LET spectra calculations. The clonogenic assay was performed using the H460 lung cancer cell line in standard 6-well plates. Using two different experimental setups, the same dose and dose-averaged LET (12.6 keV/µm) was delivered to the cell layer; however, each respective energy or LET spectrum was different. We quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous RBE measurements) events in the LET spectra separately for these two setups as 39% and 53%. 8 dose levels with 1 Gy increments were delivered. The photon reference irradiation was performed using 6 MV x-rays from a LINAC. Results: The survival curves showed that both proton irradiations demonstrated an increased RBE compared to the reference photon irradiation. Within the proton-irradiated cells, the setup with 53% dose contribution from high-LET events exhibited the higher biological effectiveness. Conclusion: The experimental results indicate that the dose-averaged LET may not be an appropriate indicator to quantify the biological effects of protons when the LET spectrum is broad enough to contain both low- and high-LET events. Incorporating the LET spectrum distribution into robust intensity-modulated proton therapy optimization planning may provide more accurate biological dose distribution than using the dose-averaged LET. NIH Program Project Grant 2U19CA021239-35

1. Mast cells cultured from human peripheral blood have been used as a cell model for functional studies of human mast cells, particularly human lung mast cells. However, the beta-adrenoceptor subtype expressed by these cultured cells has not been identified. The aim of the present study was to characterize pharmacologically the beta-adrenoceptors involved in the suppression of IgE-mediated release of mediators, including histamine, prostaglandin (PG) D2 and leukotriene (LT) C4 from cultured mast cells. 2. Mast cells were cultured from mast cell progenitors isolated from peripheral blood in the presence of 200 ng/mL stem cell factor and 50 ng/mL interleukin-6. Mast cells were sensitized with human myeloma IgE, treated with beta-adrenoceptor agonists or antagonist and then challenged with anti-human IgE. The release of histamine, PGD2 and LTC4 from mast cells was determined. 3. Both isoprenaline and salbutamol inhibited anti-IgE-induced release of histamine, PGD2 and LTC4 from cultured mast cells in a dose-dependent manner. Isoprenaline was a more potent inhibitor than salbutamol. The pD2 values for the inhibition of the release of histamine, PGD2 and LTC4 were 7.37 +/- 0.12, 8.38 +/- 0.23, 8.85 +/- 0.23, respectively, for isoprenaline and 6.96 +/- 0.12, 7.65 +/- 0.36, 7.91 +/- 0.64, respectively, for salbutamol. The selective beta3-adrenoceptor agonist BRL-37344 failed to affect anti-IgE-induced histamine release from cultured mast cells. 4. The selective beta2-adrenoceptor antagonist ICI 118 551 (108 mol/L) strongly reversed the concentration-dependent suppression of histamine release by isoprenaline and salbutamol; however, the selective beta1-adrenoceptor antagonist atenolol (106 mol/L) did not have any effect. 5. These results indicate that both isoprenaline and salbutamol act at beta2-adrenoceptors to suppress IgE-mediated mediator release from cultured human mast cells.

Mast cells cultured from human peripheral blood have been widely used to study human mast cell function. Prostanoids are the important regulators of mast cell activity, however, there were no reports about the class of prostanoid receptors expressed on such cultured cells.The present study was to characterize pharmacologically the prostanoid receptors by investigating the effects of prostanoid receptor agonists on the immunoglobulin E (IgE)-mediated histamine release from the cultured mast cells.Mast cells cultured from human progenitor cells in peripheral blood were sensitized with human myeloma IgE, and then challenged with anti-human IgE following pretreatment with diverse prostanoid receptor agonists. The histamine content in supernatants and cell pellets were measured by histamine auto-analyzer.Of the prostanoid receptor agonists tested, the prostaglandin E2 (PGE2) receptor (EP receptor) agonist PGE2 (10(-7) to 10(-11) M) produced concentration-related potentiation of IgE-mediated histamine release from the cultured mast cells. Sulprostone, an EP1/EP3 agonist, SC-46275, a selective EP3 agonist, and 11-deoxy-PGE1, a selective EP2/EP3/EP4 agonist also caused a significant increase in histamine release induced by anti-IgE. BW245C, fluprostone, cicaprost and U46619 for the prostaglandin D2, F2alpha, I2, and thromboxane A2 receptors respectively, and the EP2/EP4 receptor agonist butaprost had little effect on anti-IgE stimulated histamine release from mast cells.The present results suggest that PGE2 potentiates the IgE-mediated histamine release from the cultured mast cell via EP3 and/or EP1 receptors.

Laser Raman spectroscopy was used to detect the nature of the structural change in lysozyme sensitized by hypocrellin A (HA) at the molecular level. The results indicated that the orderly structure of lysozyme has been damaged by the active oxygen (1O2, O2−·and.OH, etc.) generated by HA, and cause the changes in H-bonds system of the main chain and the side chain of lysozyme.

The preparation, characterization and potential liquid chromatographic applications of two totally and partly functionalized β-cyclodextrin-bonded stationary phases were presented. Separation of a series of organophosphorus racemic compounds was achieved under normal and reverse-phase conditions. Separation factor was up to 1.812 and resolution up to 4.072. The influence of chromatographic conditions was investigated and the possible chiral recognition mechanism was proposed.

To investigate the clinical efficacy of Tianfoshen oral liquid (TFS) in treating moderate and advanced malignant tumors and its mechanism.Therapeutic effect of TFS in treating 71 patients of malignant tumor was analyzed with the criteria, including quality of life, 3-year survival rate and immune function. And experimental studies of inhibitory effect on tumor clone primordial cells and tumor growth rate of TFS on human gastric tumor (MGC803) cell, human liver cancer (SMMC7721) cell and mice galactophore cancer (EMT6) cell by colony forming method and dye exclusion test respectively were also conducted.Clinical study showed that in the 71 cases treated, the total remission rate was 45.1%, the effective rate 71.8%, with improvement in quality of life and immune function, the 1-, 2- and 3-year survival rate being 78.5%, 38.5% and 10.8% respectively and the mean survival time 24.2 months. Experimental study showed that TFS could kill the cancer cells directly, inhibit the proliferation of single clonogenic cell, and had a broad-spectrum dose-dependent inhibitory action on various tumors with significant difference in comparing with the effects of the control (P0.05).TFS had obvious therapeutic effect to moderate and advanced tumors, its anti-tumor effect was related to the enhancement of immune function and tumor inhibiting or direct killing action.

Two factors, is classification and its immunogenetics, may have contributed to an incomplete understanding of the pathogenic mechanism in the disease group commonly termed 'cicatricial pemphigoid'. We have previously demonstrated that pure ocular cicatricial pemphigoid (OCP) is a unique clinical and immunopathological entity. In an effort to better define the immunogenetic characteristics for patients with pure OCP, we performed HLA typing for the class II MHC gene HLA-DQB1*0301 allele, by amplifying genomic DNA extracted from patients with polymerase chain reaction, followed by hybridization with a sequence-specific oligonucleotide probe on dot-blotted and Southern-blotted amplified DNA samples. Ninety percent (9/10) of patients with pure OCP had the DQB1*0301 allele, in contrast to 52% (17/33) of normal individuals who had the DQB1*0301 allele. The high frequency of the HLA-DQB1*0301 allele in patients with pure OCP may point to a distinct immunogenetic pattern and possibly a distinct pathomechanism for the disease.

Summary form only given. Using photon echo processes a range of all-optical signal processing operations can be performed in inhomogeneously broadened materials. For example, all-optical devices for communication, such as optical bit-rate converters and routers and optical data storage devices and erasable memories with storage densities in the range of terabits/cm/sup 2/ have been proposed based on photon echo processes in rare-earth-ion-doped crystals.

We have studied by immunocytochemistry, the distribution of DMT-1, a cellular iron transporter responsible for transport of metal irons from the plasma membrane to endosomes, in the normal monkey cerebral neocortex and hippocampus. Light to moderate DMT-1 staining was observed in glial cell bodies in the neocortex, the subcortical white matter, and the hippocampus. Despite light labeling of cell bodies, glial end feet around cortical and subcortical blood vessels were heavily labeled. In the neocortex, the glial cell bodies displayed the morphological features of protoplasmic astrocytes. Labeled glial cells in the subcortical white matter contained dense bundles of glial filaments and were identified as fibrous astrocytes. The observation that DMT-1 was present on astrocytic endfeet suggests that these cells are involved in uptake of iron from endothelial cells. It is possible that the iron could then be redistributed into the extracellular space in the brain parenchyma.

Purpose: We report a hybrid scattering and scanning beam delivery approach, termed as (HimpsPT), which demonstrated that majority IMPT delivery can be potentially replaced with hybrid IMPT and PSPT delivery with similar or better plan quality. Methods: Three representative clinical cases, including head and neck (HN), skull base chordoma (CNS) and lung cancer, treated in MDACC Proton Therapy Center with IMPT were retrospectively redesigned using HimpsPT. The PSPT plans are designed with the same prescriptions as those of IMPT plans. The whole treatment can be delivered by either alternating or sequential PSPT and IMPT delivery. The dosimetric data and dose distributions of HimpsPT plans are compared with those of IMPT plans. We also performed a worst-case robust analysis for all plans. Results: The target coverages for all cases are comparable. For the HN case, the mean dose of esophagus larynx, left parotid and right submandibular, oral cavity V20, the max dose of cord is 18.0, 36.1, 23.6, 47.2, 0.1, 31.7 Gy in HimpsPT plan, and 25.5, 33.8, 24.9, 49.1, 0.2, 33.8 Gy in IMPT plan. For the lung case, the lung V5, V20, V30, mean lung dose, heart V40, esophagus V70, cord maximum dose are 50.5%, 37.0%, 31.7%, 21.3 Gy, 7.2%, 4.9%, 35.5 Gy in HimpsPT plan, and 55.4%, 36.7%, 30.1%, 21.3 Gy, 7.7%, 8.4%, 36.8Gy in IMPT plans. For the CNS case, brainstem maximum dose is 50.5 Gy in HimpsPT plan and 55.4 Gy in IMPT plan due to sharp penumbra offered by the aperture of the PSPT plan in HimpsPT technique. Conclusion: For majority disease sites, the dosimetric advantage of IMPT technique can be achieved by the hybrid PSPT and IMPT technique, which enables the centers equipped with both scattering and scanning beam facilities to treat more patients which can be benefited by the scanning beam.

Purpose: To perform dose profile and output factor (OF) measurements with the Exradin W1 plastic scintillation detector (PSD) for small fields made by the high-definition multi-leaf collimator (MLC) on the TrueBeam STx system and to compare them to values measured with an IBA CC01 ionization chamber and a Sun Nuclear Edge detector diode for 6 MV photon beams. Methods: The Exradin W1 is a new small volume near-water equivalent and energy independent PSD manufactured by Standard Imaging, Inc. All measurements were performed in an IBA Blue Phantom water tank. Square MLC-shaped fields with sides ranging from 0.5 cm to 2 cm and jawshaped fields with sides ranging from 1 cm to 40 cm were measured using an SAD setup at 10 cm depth. Dose profile and percent depth dose (PDD) measurements were also taken under the same conditions for MLC fields 0.5×0.5 and 1×1 cm2 in size with jaws at 2×2cm2. The CC01 and W1 were vertically mounted. Results: OFs measured with the W1 for jaw only square fields were consistent with the ones measured with a Farmers PTW TN33013 ion chamber (1.8% maximum deviation). OF and penumbra measurement results are presented below. PDDs measured for all detectors are within 1.5% for the 0.5×0.5 cm2 and within 1% for the 1×1 cm2 MLC fields.Output factors:MLC size W1 CC01 EDGE0.5cm 0.555 0.541 0.5851.0cm 0.716 0.702 0.7331.5cm 0.779 0.761 0.7772.0cm 0.804 0.785 0.796Penumbras (mm):MLC size W1 CC01 EDGE0.5cm 2.7 2.9 2.51.0cm 3.0 3.4 2. Conclusion: OFs measured for small MLC fields were consistent with the ones measured with the other stereotactic detectors. Measured penumbras are consistent with detector size. The Exradin W1 PSD is an excellent choice for characterizing MLC-shaped small beam dosimetry used for stereotactic radiosurgery and body radiation therapy. Sam Beddar would like to disclose a NIH/NCI SBIR Phase II grant (2R44CA153824-02A1) with Standard Imaging, Title: “Water-Equivalent Plastic Scintillation Detectors for Small Field Radiotherapy”

Purpose: The passive scattering proton therapy (PSPT) technique is the commonly used radiotherapy technique for craniospinal irradiation (CSI). However, PSPT involves many numbers of junction shifts applied over the course of treatment to reduce the cold and hot regions caused by field mismatching. In this work, we introduced a robust planning approach to develop an optimal and clinical efficient techniques for CSI using intensity modulated proton therapy (IMPT) so that junction shifts can essentially be eliminated. Methods: The intra-fractional uncertainty, in which two overlapping fields shift in the opposite directions along the craniospinal axis, are incorporated into the robust optimization algorithm. Treatment plans with junction sizes 3,5,10,15,20,25 cm were designed and compared with the plan designed using the non-robust optimization. Robustness of the plans were evaluated based on dose profiles along the craniospinal axis for the plans applying 3 mm intra-fractional shift. The dose intra-fraction variations (DIV) at the junction are used to evaluate the robustness of the plans. Results: The DIVs are 7.9%, 6.3%, 5.0%, 3.8%, 2.8% and 2.2%, for the robustly optimized plans with junction sizes 3,5,10,15,20,25 cm. The DIV are 10% for the non-robustly optimized plans with junction size 25 cm. The dose profiles along the craniospinalmore » axis exhibit gradual and tapered dose distribution. Using DIVs less than 5% as maximum acceptable intrafractional variation, the overlapping region can be reduced to 10 cm, leading to potential reduced number of the fields. The DIVs are less than 5% for 5 mm intra-fractional shifts with junction size 25 cm, leading to potential no-junction-shift for CSI using IMPT. Conclusion: This work is the first report of the robust optimization on CSI based on IMPT. We demonstrate that robust optimization can lead to much efficient carniospinal irradiation by eliminating the junction shifts.« less

Grassland ecosystem is important for climatic regulation, maintaining the soil and water. Research on the grassland monitoring method could provide effective reference for grassland resource investigation. In this study, we used the vegetation index method for grassland classification. There are several types of climate in China. Therefore, we need to use China's Main Climate Zone Maps and divide the study region into four climate zones. Based on grassland classification system of the first nation-wide grass resource survey in China, we established a new grassland classification system which is only suitable for this research. We used MODIS images as the basic data resources, and use the expert classifier method to perform grassland classification. Based on the 1:1,000,000 Grassland Resource Map of China, we obtained the basic distribution of all the grassland types and selected 20 samples evenly distributed in each type, then used NDVI/EVI product to summarize different spectral features of different grassland types. Finally, we introduced other classification auxiliary data, such as elevation, accumulate temperature (AT), humidity index (HI) and rainfall. China's nation-wide grassland classification map is resulted by merging the grassland in different climate zone. The overall classification accuracy is 60.4%. The result indicated that expert classifier is proper for national wide grassland classification, but the classification accuracy need to be improved.

The aim of this study was to evaluate the severity and patterns of fatigue during preoperative chemoradiation therapy for locally advanced rectal cancer and determine whether there are predictors for patients who develop severe fatigue.Seventy-two patients with resectable rectal cancer received chemoradiation (total radiation dose, 45 gray/25 fractions to the pelvis; continuous infusion of 5-fluorouracil [300 mg/m(2)]). The Brief Fatigue Inventory (BFI), a measure that categorizes fatigue severity on a 0-10 scale, was administered weekly during treatment. Severe fatigue was defined as 7-10 on the "worst level of fatigue" item. Demographics, disease information, toxicities, and blood counts were collected. Descriptive statistics, repeated measure analysis of variance, and multiple regression were used to examine fatigue and its correlates.Fatigue increased in 67% of patients during chemoradiation (CTX/XRT). The mean fatigue score increased from 3.16 before treatment to 4.62 at the end of treatment. A significant linear trend suggested that fatigue progressively got worse during CTX/XRT (F = 16.497, P0.001). However, 18% of patients experienced severe fatigue before CTX/XRT; this was predicted by uncontrolled pain (r(2) = 0.321; F = 16.52; P0.001). During CTX/XRT, uncontrolled diarrhea was the only predictor for increased fatigue (r(2) = 0.182; F = 7.77; P0.01). Approximately one-third of patients had severe fatigue, which impaired their function at the end of CTX/XRT.Preoperative chemoradiation therapy for patients with rectal cancer was associated with progressive fatigue during therapy. Based on identified predictors for fatigue, more active pain management before CXT/XRT and bowel management during CTX/XRT might reduce cancer-related fatigue in these patients.

The distribution of glutamate receptors in the monkey subthalamic nucleus was studied using affinity purified polyclonal antibodies to GluR1, phosphorylated GluR1, GluR2/3, NMDAR1, mGluR1a and mGluR5. Intense staining for both the unphosphorylated and the phosphorylated forms of the AMPA receptor subunit GluR1 was observed in the cell bodies and proximal dendrites of neurons in this nucleus. In comparison to GluR1, less intense staining for GluR2/3 was observed in the cell bodies and processes. NMDAR1 immunoreactivity was present in cell bodies and large numbers of small diameter dendrites. Light staining was observed in cell bodies with mGluR1a and no staining was observed on cell bodies with mGluR5. The neuropil, however, contained many processes that were labeled for mGluR1a or mGluR5. Electron microscopy showed that label was present in cytoplasmic locations in cell bodies and dendrites, in addition to components of the synaptic region, in sections stained for GluR1, GluR2/3 and NMDAR1. In contrast, very lightly labeled or unlabeled cell bodies but labeled dendrites and axon terminals, was observed in sections stained for mGluR1a and mGluR5. In addition to neural processes, occasional astrocytic processes were also labeled for mGluR5. Of the immunogold particles that were associated with components of the synaptic region, label for ionotropic glutamate receptors was mostly present on postsynaptic densities, whilst that for metabotropic glutamate receptors was mostly present in a perisynaptic location. The ratio of GluR1/GluR2 messenger RNAs has been reported to increase in the aged hippocampus (PAGLIUSI, S. R., GERRARD, P., ABDALLAH, M., TALABOT, D.CATSICAS, S. (1994) Neuroscience 61, 429-433.), and it is possible that a similar change in the ratio of GluR1 and GluR2 may occur in neurons of the subthalamic nucleus with age. It is postulated that this could result an increase in calcium permeability via AMPA receptors, and an enhancement of excitatory transmission in this nucleus.

The present study aimed to elucidate the distribution of the GABA transporter GAT-3 in the monkey basal ganglia and brainstem. Very dense GAT-3 immunoreactivity was observed in the medial septum, diagonal band, basal nucleus of Meynert, thalamus, globus pallidus, and substantia nigra. Moderate levels were observed in the subthalamic nucleus, periaqueductal grey, spinal trigeminal and vestibular nuclei. A general light level of staining was observed in the remainder of the brainstem regions, and very light staining was observed in the caudate nucleus and putamen. Electron microscopy showed that GAT-3 immunoreactivity was present in cell bodies with light cytoplasm and dense bundles of glial filaments, and features of astrocytes. Large numbers of astrocytic processes were also labeled in the neuropil. The cell bodies and processes of neurons were unlabeled. Further study is necessary to elucidate GAT-3 expression in neurological conditions, including hyperalgesia and Parkinson's disease.

The distribution of the GABA transporter GAT-1 was studied by immunocytochemistry and electron microscopy in the monkey basal ganglia. Dense staining was observed in the globus pallidus externa and interna, intermediate in the subthalamic nucleus, and substantia nigra, and light staining in the caudate nucleus and putamen. Staining was observed in axon terminals, but not cell bodies. Electron microscopy showed that the GAT-1 positive axon terminals formed symmetrical synapses, suggesting that they were the terminals of GABAergic neurons. Comparison of areas high in GAT-1 protein with that of GABA showed a good correlation between the density in neuropil staining for GAT-1, and that of GABA.

The purpose of this project was to develop the M. D. Anderson Symptom Inventory (MDASI), a brief measure of the severity and impact of cancer-related symptoms.A list of symptoms was generated from symptom inventories and by panels of clinicians. Twenty-six symptoms and 6 interference items were rated by a validation sample of 527 outpatients, a sample of 30 inpatients from the blood and bone marrow transplantation service, and a cross-validation sample of 113 outpatients. Clinical judgment and statistical techniques were used to reduce the number of symptoms. Reliability, validity, and sensitivity of the MDASI were examined.Cluster analysis, best subset analysis, and clinical judgment reduced the number of symptoms to a "core" list of 13 that accounted for 64% of the variance in symptom distress. Factor analysis demonstrated a similar pattern in both outpatient samples, and two symptom factors and the interference scale were reliable. Expected differences in symptom pattern and severity were found between patients with "good" versus "poor" performance status and between patients in active therapy and patients who were seen for follow-up. Patients rated fatigue-related symptoms as the most severe. Groups of patients classified by disease or treatment had severe symptoms that were not on the "core" list.The core items of the MDASI accounted for the majority of symptom distress reported by cancer patients in active treatment and those who were followed after treatment. The MDASI should prove useful for symptom surveys, clinical trials, and patient monitoring, and its format should allow Internet or telephone administration.

The health-related functioning of patients with cancer is compromised by several factors, including the disease process, treatment, and the various symptoms that are produced by both disease and treatment. This study was designed to specify the relationship between patients' pain severity and their self-reported quality of life.The study enrolled 216 consecutive consenting adult patients from 2 Chinese cancer centers with pathologically-diagnosed metastatic cancer who could understand and complete the self-report measures. The majority had cancer-related pain and were receiving analgesics. The Chinese version of the Brief Pain Inventory was used to assess the severity and interference of pain. A Chinese translation of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used to assess health-related functional status. Patients' physicians completed a form that indicated characteristics of the patients' cancer, Eastern Cooperative Oncology Group performance status, pain, and current pain treatment.Increasing severity of pain was associated with worsening health-related functioning, even when an estimate of disease severity was taken into account. The correlation between pain severity and impairment was nonlinear. The functional health and well-being of cancer patients with no or mild pain was significantly less impaired than that of patients with moderate or severe pain. The impairment of patients with moderate and severe pain did not differ.Pain severity is an important variable to be taken into account when quality of life outcome measures are considered. The functioning of cancer patients with well-controlled (mild) pain did not differ significantly from that of patients without pain. Providing pain relief should significantly improve the functional status of cancer patients.

Fatigue is a major disease and treatment burden for cancer patients. Several scales have been created to measure fatigue, but many are long and difficult for very ill patients to complete, or they are not easy to translate for non-English speaking patients. The Brief Fatigue Inventory was developed for the rapid assessment of fatigue severity for use in both clinical screening and clinical trials.The study enrolled 305 consecutive, consenting adult inpatients and outpatients with cancer who could understand and complete the self-report measures used in the study. The same instruments also were administered to 290 community-dwelling adults to obtain a comparison sample. Research staff completed a form that indicated the primary site and stage of the cancer, rated the Eastern Cooperative Oncology Group performance status of the patient, described the characteristics of the pain, and described the current pain treatment being provided to the patients.The BFI was shown to be an internally stable (reliable) measure that tapped a single dimension, best interpreted as severity of fatigue. It correlated highly with similar fatigue measures. Greater than 98% of patients were able to complete it. A range of scores defining severe fatigue was identified.The BFI is a reliable instrument that allows for the rapid assessment of fatigue level in cancer patients and identifies those patients with severe fatigue.

Purpose: To characterize neutron dose equivalent per proton Gray (H/D) as a function of proton energy, spread‐out Bragg peak (SOBP) and aperture size at a clinical proton treatment facility using both active and passive neutron detection instruments, and to evaluate the performance of the instruments for a possible candidate for routine patient neutron exposure monitoring. Method and Materials: The H/D were measured at 2 locations near isocenter, namely in proton field but 2 cm out of range and approximately 20 cm out of field, with neutron instruments of various types. Two types of rem‐meters were used, the REM‐500, a tissue equivalent proportional counter and SWENDI‐2, a wide energy (up to 5GeV) neutron probe. The passive detectors consist of Neutrak® 144 Fast, Intermediate and Thermal Neutron Dosimeters, an etched‐track detector, and two flavors of bubble detector, BDS®, a spectrometer, and BD‐PND®. The results from these instruments were compared for 200 MeV and 160 MeV beam configurations. REM‐500 and Neutrak® were used to study the dependency of H/D on proton energy, SOBP and aperture size. Results: Various instruments had comparable H/D measurements at the out field location but varies more at the in field location. The H/D value increased linearly with proton energy, with a factor of ∼6 from 100 MeV to 250 MeV for medium snout. The H/D value increased ∼50% with increasing SOBP from 2 cm to the maximum of clinical allowed value and had a small decrease with aperture size. Conclusion: The measured results show H/D increases strongly with proton energy, moderately with SOBP, and has minimal dependence on aperture size. This is consistent with the simulation results. The Neutrak® etched‐track detector is a good candidate for patient neutron exposure monitoring due to its small size, excellent dose range, good energy range and commercial support.

Mitogen-activated protein kinase (MAPK) kinases (MKKs) are dual-specificity protein kinases that phosphorylate and activate MAPK. We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open reading frame of 347 amino acids with 11 kinase subdomains. MKK7 is ubiquitously expressed in all adult and embryonic organs but displays high expression in epithelial tissues at later stages of fetal development. When transiently expressed in 293 cells, MKK7 specifically activated stress-activated protein kinases (SAPKs)/c-Jun N-terminal protein kinases (JNKs) but not extracellular-regulated kinase or p38 kinase. A kinase-negative mutant of MKK7 inhibits interleukin-1beta, lipopolysaccharide, and MEKK1-induced SAPK/JNK activation. Thus, MKK7 is a new member of the MAPK kinase family that functions upstream of SAPK/JNK in the SAPK/JNK signaling pathway.

Apolipoprotein E (apoE) and certain peptides derived from it have been shown to exert neurotoxic effects in vitro, and apoE has been linked to the etiology of Alzheimer's disease. The mechanisms underlying these toxic and pathological effects are, however, not known. To approach this question, we have studied the effects of apoE peptides on the cytoplasmic calcium ([Ca2+]i) homeostasis of cultured cortical neurons. A tandem dimer repeat peptide (apoEdp) derived from the receptor binding domain of apoE was found to have a potent effect on elevation of [Ca2+]i calcium. The pathway by which apoEdp exerted this effect was shown to involve both the mobilization of intracellular calcium and the influx of extracellular calcium, although the effect on influx was more pronounced. Calcium mobilization occurs via a G-protein-linked phospholipase C (PLC) pathway, whereas calcium influx appears to involve a novel Co2+-sensitive channel. Both the mobilization and the influx of calcium require the binding of the apoE peptide to a membrane receptor because both pathways are blocked by antibody to low-density-lipoprotein receptor-related protein. The data suggest that the neurotoxic effects of apoE may be mediated by a persistent elevation of [Ca2+]i.

Summary. To evaluate Fas/FasL expression in hepatitis B virus-related chronic liver disease, liver biopsies from 44 such cases were studied immunohistochemically. FasL was detected in the infiltrating lymphocytes and both FasL and Fas were found in the hepatocytes. The Fas and FasL-positive cells were mostly found at the advancing edges of interphase hepatitis, and Fas/FasL expression was closely correlated with the inflammatory activity. Unexpectedly, FasL was also expressed in liver cirrhotic nodules, particularly in those with hepatocellular carcinoma with or without inflammation. These results suggest that the factors which induce hepatocyte transformation might also trigger FasL expression and promote FasL/Fas-mediated apoptosis.

Purpose: The purpose of this study is to determine whether the inter‐fractional motion of the anatomy has a more significant impact on proton dose distributions compared to IMRT dose distributions. A secondary objective is to evaluate the impact of CTV‐to‐PTV margins on plans for protons produced with the double scattering technique. Method and Materials: Repeat CT scans of prostate patients acquired with a CT‐on‐Rails were used for this study. First, proton and IMRT plans were designed using (1) the CTV‐to‐PTV margin standard at our institution (normally 8 mm except at the rectum‐prostate interface, where it is 5.8 mm) and (2) a small uniform margin (3mm). The proton and IMRT plans were then applied to 8 daily CTimages aligned either to skin marks or the center of prostate. The doses for the 8 daily CTimages were recalculated using the same beam configurations (aperture, compensators, gantry angles, Monitor Units etc). Results: For proton plans, a 3mm margin appears to be adequate for tumor coverage even when a conventional skin mark alignment technique is used. The proton plans with 3mm margins lead to nearly the same coverage as in the IMRT plans with standard margins. For prostate center of volume‐based alignment, this coverage was 98.6% for protons vs. % 98.1 for IMRT and 96.6% vs. 96.3% for skin marks‐based alignment. Conclusion: With the double scattering technique, the dose distribution from the proton plan is not very sensitive to the daily variation of the patient anatomy as compared to IMRT plans. The 3 mm CTV‐to‐PTV margin is acceptable for proton plans but not for IMRT plans for both alignment methods. The preliminary data show that the CTV‐to‐PTV margin can be reduced to 3mm if we use daily image guided set‐up.

Patients with colorectal cancer (CRC) report debilitating fatigue that is caused by both disease and chemotherapy. An inflammatory mechanism for fatigue and affective symptoms has been proposed in cancer patients. This prospective study investigated tryptophan and tyrosine metabolism and symptom severity in 33 CRC patients undergoing oxaliplatin-based chemotherapy. During the 12-week study, patients rated symptom severity weekly using the M.D. Anderson Symptom Inventory (MDASI). Serum samples were collected before and after 3 and 6 chemotherapy cycles. Fatigue was the most severe patient-reported symptom before and during chemotherapy. Non-parametric generalized regression models were used to assess correlations between symptom severity and markers of guanosine triphosphate cyclohydrolase 1 (GTP-CH1) and indoleamine-2,3-dioxygenase (IDO) activity. At week 12, the kynurenine/tryptophan ratio was significantly associated with fatigue and sadness (both p

Purpose: To investigate advantages of SIB technique using IMPT for advanced stage NSCLC Method: The 4DCT data sets were randomly selected from 9 patients with stage IIINSCLC. The SIB volume (SIBV) was defined as GTV with 3mm expansion to account for uncertainties. PTV was defined as CTV with 5mm expansion. Conventional IMPT plan delivering 74Gy/37Fractions to at least 95% of PTV and IMPT SIB plans delivering 72Gy (BED:89.3Gy), 78Gy (BED:98.3Gy) and 84Gy (BED:107.5Gy) in 30 fractions to at least 95% of SIBV as well as 60 Gy to at least 95% of PTV were designed for each patient using robust optimization. TCP and NTCP were calculated and worst case robustness was analyzed for one patient. Results: The NTCP for lung and esophagus were 0.02 and 0.38 respectively for IMPT SIB 72Gy, 0.1 and 0.32 lower than those for IMPT 74Gy respectively, while TCP of PTV and SIBV are 0.87 and 0.9 for IMPT 74Gy, and 0.89 and 0.9 for IMPT SIB 72Gy respectively. The dose coverage of CTV and GTV in worst scenario was at least 95% of prescribed dose for both IMPT SIB 72Gy and IMPT 74Gy plans. The comparison of IMPT SIB plans showed no significant differences of normal structures sparing at different escalation dose level, such as percentage lung volume received 20Gy (V20, 29%) and mean dose (20Gy), esophagus V60 (16%), and maximum cord dose (36Gy). Our results suggest that dose escalation to SIBV only (TCP of SIBV are 0.9, 0.93 and 0.95 for SIB dose level 72Gy, 78Gy and 84Gy) in IMPT SIB technique will have minimal impact for normal structures sparing. Conclusion: IMPT SIB showed significantly advantages in target dose escalation with minimal impact on normal structures sparing. We are currently testing the impact of IMPT SIB on patient outcome in a prospective trial.

Purpose: To investigate uncertainties of patient setup for electron boost field using an in‐house breast compression device for breast cancer irradiation. Method: Ten early stage breast cancer patients with deep seated tumor beds treated with post‐lumpectomy radiation were randomly selected. The patients underwent resimulation and treatment with the compression device to decrease the depth of tumor bed. A cone beam computed tomography (CBCT) scan was performed for each patient before treatment and fused with the simulation CT. Four surgical clips located in superior, inferior, left and right of tumor bed were identified in both CT and CBCT data sets for each patient. Set‐up uncertainties were estimated based on differences in the positions of the clips between scans relative to the marked isocenter. Results: For each patient, all clips shifted consistently in the same direction superior‐inferior (SI) and left‐right (LR) direction, but not in the anterior‐posterior (AP) direction because of the perturbation of the compression device. 50% of clips (20 out of 40 clips) shifted anteriorly, 60% shifted inferiorly, and 70% shifted left. Clip shifts in AP direction were smaller than in SI and LR direction. The 55% of clips shifted >1 cm, 18% of clips shifted > 1.5 cm, and only one clip shifted > 2cm which was out of the intended isodose coverage. The average shift of 4 clips for each patient in LR direction was correlated with the breast volume (R2=0.406), but the average shifts of 4 clips in AP and SI direction were not correlated breast volume (R2>0.02). Conclusion: For most patients whose breast boosts were treated with a compression device, a 2cm margin was sufficient to ensure target coverage based on set‐up uncertainties observed in this study. A larger margin might be necessary for electron boost fields for patients with large (volume >2000cc) and/or pendulous breasts.

Purpose: To develop a pointer based quality assurance (QA) procedure that quickly verifies the congruence of ExacTrac® image isocenter with the radiation isocenter of a linear accelerator(linac), and use it to study the accuracy and reliability of the ExacTrac® image isocenter. Method and Materials: A 6 mm diameter tungsten ball was aligned with the room laserusing a pointer alignment system. By measuring the positions of ExacTrac®image isocenter and linac radiation isocenter relative to the ball, thedeviations between the two isocenters was easily calculated. The ExacTrac®image isocenter relative to the ball was measured using the built‐in Winston‐Lutz Pointer test, in which kV images of the ball are projected to flat panels and the center of the ball to the image isocenter are calculated by ExacTrac® software. The linac radiation isocenter relative to the ball was measured by taking the portal images of the ball at four gantry angles, 0,90, 180 and 270 with a 6 × 6 cm2 field. An in‐house developed software was used to identify the center of the ball and the center of the radiation. This procedure was used in weekly QA for a year in this work. Results: A simple QA procedure was developed to ensure the accuracy of ExacTrac® imageisocenter against the linac radiation isocenter. The procedure can be executed in less than 20 minutes. The data show the position error were ‐ 0.27±0.30, 0.52±0.24, 0.18±0.22 mm in the lateral, vertical and longitudinal directions, and the max deviation were 0.86, 0.89 and 0.54 mm respectively. Conclusion: The weekly verification data showed the ExacTrac® image isocenter can be very reliable with sub‐millimeter accuracy. This level of imaging alignment accuracy is necessary for imaging guided SBRT procedures. The quick QA procedure can be applied on‐demand to ensure the accuracy of ExacTrac® isocenter.

In contrast to the horse heart apocytochrome c, the chicken heart apocytochrome c underwent a conformational change from random coil to partial folding during a renaturation process. When the apocytochrome horse heart and that of chicken heart c were subjected to a translocation assay in vitro using large trypsin-enclosed unilamellar vesicles from soybean phospholipids, the ability of the chicken heart apocytochrome c to penetrate into the liposomes was found to decrease markedly with the renaturation procedure, while that of horse heart apocytochrome c remained relatively constant. Observations from circular dichroism measurement on the induction of secondary folding of these two species of apocytochrome c upon interaction with soybean phospholipid vesicles suggested that a more flexible structure of apocytochrome c embedded in the lipid matrix be required for its efficient translocation across the bilayer.

Purpose: To improve the accuracy of small MLC field and penumbra dose calculation by refining 6 MV beam model for IMRT‐based SBRT. Methods: A new dataset of depth and detector size corrected beam profiles of both jaw and MLC‐collimated fields were measured to refine a Pinnacle beam model for a Varian linac. Specific beam modeling sequence was used to tune the output factor for MLC‐collimated fields. In addition, the rounded leaf radius was also used as a free parameter for the new beam model. Previous IMRT patient QA data were also used for the verification of the new beam model and fine turning the MLC modeling parameters. The clinical impact of the refined model was studied by investigating the agreement of QA measurement with the new beam model. Results: Tests in MLC‐collimated fields showed our current beam model consistently over‐estimate the dose by as much as 4% for small MLC fields ranging between 2cm to 5cm with a large jaw opening. A refined new model with detector size corrected profiles required a smaller effective source size and a larger head scatter than the current beam model. We found the new model was able to reduce the IMRT QA discrepancies both in ion chamber and film measurements for SBRT of spine patients. Interestingly, our beam modeling process significantly improved the QA result for small field IMRT without affecting the QA result for large field IMRT cases. Conclusions: A more accurate Pinnacle beam model can be derived from the detector size corrected profiles, MLC‐collimated small field measurements, and the use of large amount of historical QA measurement data. The new beam model will benefit for intensity modulated spinal stereotactic radiosurgery or other small field IMRT applications.

Purpose: To evaluate the dosimetric effect of spine hardware on intensity modulated spinal sterotactic radiosurgery (IMSRT) treatment planning in Pinnacle. Methods: Monte Carlo(MC) modeling of a clinical 6 MV photon beam was validated with measured Percentage depth dose (PDD) and cross profile for various field sizes. Once validated, MC simulation was used to study the dosimetric effect of a 5‐mm diameter Titanium rod in water for field sizes 2×2, 3×3 and 5×5 cm2. We used MC results to benchmark the Pinnacle treatment planning system on heterogeneity calculations for Titanium rods by overriding the titanium density (4.5 g/cm3) from the default CT‐Density LUT value of 1.75 g/cm3. Finally, Pinnacle was used to study the dosimetric effect of metal implant in IMSRT plan by evaluating the DVH difference between a hardware density of 1.75 and 4.5. In the study, spine hardware was auto contoured and verified with DCR in multiple beam angles. Results: Pinnacle's heterogeneity calculation for titanium rods are accurate when relative electronic density of 4.5 is used based on our benchmark tests using MC simulations. Overriding the hardware density from 1.75 to 4.5 decreases the dose to the part of the target that is blocked by the hardware, which reduces the target volume that receives the prescribed dose. For the 7 cases we evaluated, the reduction of target volume receiving the prescription dose can be as high as 15% with most cases around 4%. The dosimetric effect of the hardware on critical structures, such as cord, is minimal. Conclusions: Our results showed metal implants can cause significant dose perturbations in spine SBRT. Beam angle selection should minimize the presence of the metal hardware in the beam path. Appropriate density values should be used for the hardware to improve the dose calculation accuracy.

Purpose: To explore advantages and uncertainties of IMPT for accelerated partial breast irradiation (APBI), and compare the dosimetry with passive scatteringprotons (PSPB) and clinic photon 3D radiotherapy (3DCRT). Method and Materials: Two theoretical proton IMPT plans, i.e. one with two tangential fields (OPPOSED_PAIR) and one with a tangential field and an en face field (ORTHOGONAL_PAIR), were created for 11 patients and compared with PSPB and 3DCRT. The impact of range and patient setup uncertainties and scanned spots mismatching between fields for IMPT plans was evaluated. Results: Compared with 3DCRT, IMPT plans with both beam configurations significantly reduced the dose to lungs, normal breast tissues,heart and breast skin and have significantly better dose coverage for target volume using ORTHOGONAL_PAIR and comparable coverage using OPPOSED_PAIR. Compare with PSPB, IMPT with both beam configurations was significantly better for V90 and V75 of breast skin, and V90 and V75 of ipsilateral normal breast, and comparable for V50 and V30 of breast skin, V100 of ipsilateral normal breast, V5Gy and mean dose of ipsilateral lung, maximum dose of heart and contralateral breast, and mean dose of contralateral lung. IMPT using ORTHOGONAL_PAIR was comparable for V10 of breast skin, V50 and V20 of ipsilateral normal breast, and V10Gy and V20Gy of ipsilateral lung, but significantly worse using OPPOSED_PAIR. For IMPT, CTV coverage of 95% prescription dose was over 90% considering range and patients setup uncertainties, but could drop to 80% with scanned spots mismatching between two beams in worst scenario. The en face beam has significantly more dose fluctuation in chestwall region than tangential beam. Conclusion: IMPT plans showed potential for normal tissuedose reduction and target coverage improvement compared with PSPB and 3DCRT. It is robust considering range and patient setup uncertainties, but vulnerable to the scanned spots mismatching among different beams.