bluuebunny/crossref_metadata_2025_split huggingface dataset:
TU‐EE‐A3‐03: Performing Concurrent Kilovoltage Imaging While Delivering Megavoltage Treatment Beams
Authors: Yin F , Yoo S , Wu Q 
Published: July 2007

Purpose: To investigate the clinical feasibility of performing concurrent kilovoltage (kV) x‐ray imaging while the patient at the treatment position was irradiated by megavoltage (MV) beams. Method and Materials: Anatomical visibility and contrast details in kV images acquired with and without concurrent MV irradiations were compared. An on‐board imager (OBI) mounted to the gantry of a Varian 21EX Linac with an electronic portal imager (EPI) was used in this study. A pelvis (Rando) and a contrast (Vegas) phantoms were placed near the treatment isocenter with a detector‐to‐isocenter distance of 50 cm. The effect of MV beam and its dose rate on noise‐to‐signal ratio (NSR), defined as the ratio of the standard deviation to the mean pixel value in a region‐of‐interest (ROI), and relative contrast, defined as the ratio of mean pixel values between the signal ROI and the background ROI, were studied based on Vegas phantom. Results: Scattering MV beams and electronic noises due to kV detector scanning rate and MV beam pulse rate are two major factors affect the concurrent kV image quality. The calculated NSR increases as dose rate increases. Compared to kV images without concurrent MV irradiation, the NSRs of the contrast phantom were increased by a factor of 2.6 with 300MU/min MV beams and 4.5 with 600MU/min MV beams. However, the relative contrasts were increased by a factor of 1.02 with 300MU/min MV beam and 1.06 with 600MU/min MV beam. Conclusion: It is clinically feasible to acquire concurrent kV images during treatment with MV beams. The kV image quality may be improved by minimizing MV scattering effect and by correcting electronic noises. The ability to take kV images with concurrent MV irradiation allows real‐time verification and tracking of moving target during the gated treatment.Partially supported by a research grant from Varian Medical Systems.
TU‐EE‐A1‐01: Validation of a Prototype Deterministic Solver for Photon Beam Dose Calculations On Acquired CT Data in the Presence of Narrow Beams and Heterogeneities
Authors: Wareing T , Vassiliev O , Failla G , Davis I , McGhee J , Barnett D , Horton J , Mourtada F 
Published: July 2007

Purpose: To evaluate a deterministic method for solving the neutral and charged particle transport equations in cases where electron disequilibrium is significant. Methods and Materials: A prototype deterministic solver, Acuros®, has been developed and validated for photon beam radiotherapy. Acuros is based on the Attila® radiation transport code, which solves the differential form of the linear Boltzmann transport equation for neutral particles, and the linear Boltzmann‐Fokker‐Plank transport equation for charged particles. The angular and energy dependent photon and electron flux is solved at every spatial unknown in the computational domain, and quantities such as dose‐to‐medium (DM) are obtained by multiplying the energy dependent particle flux by the energy dependent energy deposition cross section for the associated image pixel material. Comparisons were made with the Monte Carlo code EGSnrc (DOSXYZnrc) for a head‐and‐neck case having eight 1.5×1.5 cm2 photon beams with a 6 MV photon spectrum. The Acuros calculation used 123,000 elements. Since four spatial unknowns were solved in each element, this equated to 492,000 spatial degrees of freedom.The DOSXYZnrc calculation used 2.5×2.5×2.5 mm3 voxels. Results: Results were compared at 95,183 image pixels where dose > 5% of Dmax. 99.02% of pixels satisfied the 3%/3mm criteria (94,251 out of 95,183 pixels). Computational times for the Acuros and DOSXYZnrc calculations were approximately 19.6 CPU minutes (2.2 GHz Opteron processor)and 2,890 CPU minutes (0.4% avg. uncertainty in voxels > Dmax/2), respectively. Through a rewritten, radiotherapy specific solver, Acuros computational times were further reduced to 7.45 CPU minutes without affecting accuracy. When only doses in regions greater than 20% of Dmax are of interest, computational times are further reduced to 3.08 CPU minutes. Conclusions: A clinically viable combination of dose calculation speed and accuracy has been achieved using a radiotherapy specific deterministic solver.Research funded in part by NIH grant 1R43 CA105806‐01A1.
Novel Use of Legendre Transformation in Field Theory and Many Particle Systems
Authors: Fukuda Reijiro , Komachiya Masahiro , Yokojima Satoshi , Suzuki Yoko , Okumura Ko , Inagaki Takeshi 
Published: July 2007

The Legendre transformation is one of the ways to rewrite the theory by small number of selected variables. It leads naturally to the generalized action functional called the effective action and everything starts from this generating functional. It is applied to various problems of physics ranging from the relativistic field theory to the condensed matter physics. The main techniques used here are the on-shell expansion and the inversion method.
The scheme presented in this article is thus a generating functional formalism of the many particle systems.
Expression of Ral GTPases, Their Effectors, and Activators in Human Bladder Cancer
Authors: Smith Steven Christopher , Oxford Gary , Baras Alexander S. , Owens Charles , Havaleshko Dmytro , Brautigan David L. , Safo Martin K. , Theodorescu Dan 
Published: July 2007

Abstract
Purpose: The Ral family of small G proteins has been implicated in tumorigenesis, invasion, and metastasis in in vitro and animal model systems; however, a systematic evaluation of the state of activation, mutation, or expression of these GTPases has not been reported in any tumor type.
Experimental Design: We determined the activation state of the RalA and RalB paralogs in 10 bladder cancer cell lines with varying Ras mutation status. We sequenced RalA and RalB cDNAs from 20 bladder cancer cell lines and functionally evaluated the mutations found. We determined the expression of Ral, Ral activators, and Ral effectors on the level of mRNA or protein in human bladder cancer cell lines and tissues.
Results: We uncovered one E97Q substitution mutation of RalA in 1 of 20 cell lines tested and higher Ral activation in cells harboring mutant HRAS. We found overexpression of mRNAs for RalA and Aurora-A, a mitotic kinase that activates RalA, in bladder cancer (both P &lt; 0.001), and in association with tumors of higher stage and grade. RalBP1, a canonical Ral effector, mRNA and protein was overexpressed in bladder cancer (P &lt; 0.001), whereas Filamin A was underexpressed (P = 0.004). We determined that RalA mRNA levels correlated significantly with protein levels (P &lt; 0.001) and found protein overexpression of both GTPases in homogenized invasive cancers. Available data sets suggest that RalA mRNA is also overexpressed in seminoma, glioblastoma, and carcinomas of the liver, pancreas, and prostate.
Conclusion: These findings of activation and differential expression of RalA and RalB anchor prior work in model systems to human disease and suggest therapeutic strategies targeting both GTPases in this pathway may be beneficial.
A Phase I Safety and Pharmacologic Study of a Twice Weekly Dosing Regimen of the Oral Taxane BMS-275183
Authors: Bröker Linda E. , Veltkamp Stephan A. , Heath Elisabeth I. , Kuenen Bart C. , Gall Helen , Astier Ludovic , Parker Susan , Kayitalire Louis , Lorusso Patricia M. , Schellens Jan H.M. , Giaccone Giuseppe 
Published: July 2007

Abstract
Purpose: BMS-275183, an orally administered C-4 methyl carbonate paclitaxel analogue, showed promising activity in a phase I trial investigating a weekly treatment regimen, but was associated with a relatively high incidence of neuropathic side effects. The current dose escalation phase I trial was initiated to investigate whether twice weekly administration of BMS-275183 would improve its safety and tolerability. Additionally, the pharmacokinetics and possible antitumor activity were studied.
Experimental Design: A cycle consisted of 4 weeks (i.e., eight twice weekly oral doses). The starting dose was 60 mg/m2 and the dose was increased by 20 mg/m2 increments. Cohorts consisted of three patients and were expanded to at least six patients when toxicity was encountered. Plasma pharmacokinetics were done on days 1 and 15.
Results: A total of 38 patients were enrolled. The maximum tolerated dose was 100 mg/m2 twice weekly. Seventeen patients were treated at the maximum tolerated dose; 3 of 17 patients experienced a dose-limiting toxicity, consisting of a combination of neutropenia, neuropathy, and diarrhea. BMS-275183 seemed to have a considerably lower incidence of neuropathic side effects compared with the weekly treatment regimen. Confirmed partial responses were observed in two patients with non–small cell lung cancer, one patient with prostate cancer, and one patient with melanoma. In addition, a long-lasting prostate-specific antigen response was observed in a patient with prostate carcinoma with nonmeasurable disease.
Conclusions: BMS-275183 is preferably given in a twice weekly regimen and has considerable antitumor activity. A phase II trial in non–small cell lung cancer using the twice weekly schedule has been initiated.
Cytochrome P450 17A1 and Catechol O-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland
Authors: Campbell Peter T. , Edwards Laura , McLaughlin John R. , Green Jane , Younghusband H. Banfield , Woods Michael O. 
Published: July 2007

Abstract
Purpose: Lynch syndrome is a cancer predisposition syndrome which includes colon cancer. It is caused by inherited defects in DNA mismatch repair genes. Sporadic colon cancers are influenced by exogenous hormones (e.g., postmenopausal hormones); we hypothesized that polymorphisms which influence endogenous hormones would therefore modify age at colon cancer onset among Lynch syndrome mutation carriers.
Experimental Design: We genotyped 146 Caucasian Lynch syndrome mutation carriers for a 5′-untranslated region polymorphism in cytochrome P450 17A1 (CYP17; c.−34T→C) and an exon 4 polymorphism in catechol O-methyltransferase (COMT; c.472G→A); 50 mutation carriers had developed colon or rectal cancer at last contact. We used χ2 tests to assess differences in counts. Kaplan-Meier survival curves and Cox proportional hazard models assessed age at onset of colorectal cancer stratified by CYP17 and COMT genotypes.
Results: Homozygous carriers of the CYP17 C allele were diagnosed with colorectal cancer 18 years earlier than homozygous carriers of the T allele. Hazard ratios identified that, relative to homozygous carriers of the T allele (T/T), carriers of one copy (T/C) and two copies (C/C) of the rare allele were, respectively, at 1.9-fold and 2.9-fold increased the risk of colon cancer at any age. The COMT rare allele suggested a nonstatistically significant trend of decreased colon cancer risk.
Conclusions: This study showed that a polymorphism in CYP17 (c.−34T→C) modifies age at onset of Lynch syndrome. Because of the high risk of colorectal cancer among this group, knowledge of the CYP17 genotype is warranted for genetic counseling and risk assessment. Future work should assess polymorphisms associated with steroid hormones in Lynch syndrome mutation carriers.
An Imageable Metastatic Treatment Model of Nasopharyngeal Carcinoma
Authors: Liu Tengfei , Ding Yanqin , Xie Weibing , Li Zuguo , Bai Xiaoyan , Li Xin , Fang Weiyi , Ren Caiping , Wang Shuang , Hoffman Robert M. , Yao Kaitai 
Published: July 2007

AbstractPurpose: Nasopharyngeal carcinoma is highly prevalent in southern China and is often resistant to current treatment options.Experimental Design: Clinically relevant mouse models are necessary for further understanding and drug discovery in this disease. Two nasopharyngeal carcinoma cell lines, stably expressing green fluorescent protein (GFP), 5-8F-GFP and 6-10B-GFP, were established. The cells were orthotopically injected into the nasopharynx or ectopically into the subcutis of nude mice. Whole-body fluorescence imaging was used to monitor the growth of the primary tumor as well as angiogenesis and metastasis.Results: The metastatic behavior of 5-8F and 6-10B were distinct in the orthotopic model. Orthotopic implantation of highly metastatic 5-8F cells resulted in brain invasion, cervical lymph node metastases, and pulmonary metastases similar to what is often observed in patients. Cell line 6-10B was less metastatic, which occasionally resulted in pulmonary metastasis. GFP enabled imaging of micrometastasis. Neither 5-8F nor 6-10B were metastatic in the s.c. site. These results indicated that, in addition to the cancer cell type, the host microenvironment was critical for metastasis to occur consistent with the “seed-and-soil” hypothesis. 5-8F was highly sensitive to 5-fluorouracil (5-FU), whereas 6-10B was moderately sensitive.Conclusions: The imageable orthotopic model should play a critical role in elucidating the mechanisms involved in the growth, progression, metastasis, and angiogenesis of nasopharyngeal carcinoma and for evaluation of novel compounds with potential efficacy.
Determining Risk of Biochemical Recurrence in Prostate Cancer by Immunohistochemical Detection of PTEN Expression and Akt Activation
Authors: Bedolla Roble , Prihoda Thomas J. , Kreisberg Jeffrey I. , Malik Shazli N. , Krishnegowda Naveen K. , Troyer Dean A. , Ghosh Paramita M. 
Published: July 2007

Abstract
Purpose: A considerable fraction of patients who undergo radical prostatectomy as treatment for primary prostate cancer experience biochemical recurrence detected by elevated serum levels of prostate-specific antigen. In this study, we investigate whether loss of expression of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and the phosphorylated form of the cell survival protein Akt (pAkt) predicts biochemical recurrence.
Experimental Design: Expression of PTEN and pAkt was detected by immunohistochemistry in paraffin-embedded prostate cancer tissue obtained from men undergoing radical prostatectomy. Outcome was determined by 60-month follow-up determining serum prostate-specific antigen levels.
Results: By itself, PTEN was not a good predictor of biochemical recurrence; however, in combination with pAkt, it was a better predictor of the risk of biochemical recurrence compared with pAkt alone. Ninety percent of all cases with high pAkt and negative PTEN were recurrent whereas 88.2% of those with low pAkt and positive PTEN were nonrecurrent. In addition, high Gleason scores resulted in reduced protection from decreased pAkt and increased PTEN. By univariate logistic regression, pAkt alone gives an area under the receiver-operator characteristic curve of 0.82 whereas the area under the receiver-operator characteristic curve for the combination of PTEN, pAkt, and Gleason based on a stepwise selection model is 0.89, indicating excellent discrimination.
Conclusions: Our results indicate that loss of PTEN expression, together with increased Akt phosphorylation and Gleason score, is of significant predictive value for determining, at the time of prostatectomy, the risk of biochemical recurrence.
Adeno-Associated Virus–Mediated Antiangiogenic Gene Therapy with Thrombospondin-1 Type 1 Repeats and Endostatin
Authors: Zhang Xuefeng , Xu Jianfeng , Lawler Jack , Terwilliger Ernest , Parangi Sareh 
Published: July 2007

Abstract
Purpose: Recombinant adeno-associated virus (rAAV)-mediated antiangiogenic gene therapy offers a powerful strategy for cancer treatment, maintaining sustained levels of antiangiogenic factors with coincident enhanced therapeutic efficacy. We aimed to develop rAAV-mediated antiangiogenic gene therapy delivering endostatin and 3TSR, the antiangiogenic domain of thrombospondin-1.
Experimental Design: rAAV vectors were constructed to express endostatin (rAAV-endostatin) or 3TSR (rAAV-3TSR). The antiangiogenic efficacy of the vectors was characterized using a vascular endothelial growth factor (VEGF)-induced mouse ear angiogenesis model. To evaluate the antitumor effects of the vectors, immunodeficient mice were pretreated with rAAV-3TSR or rAAV-endostatin and received orthotopic implantation of cancer cells into the pancreas. To mimic clinical situations, mice bearing pancreatic tumors were treated with intratumoral injection of rAAV-3TSR or rAAV-endostatin.
Results: rAAV-mediated i.m. gene delivery resulted in expression of the transgene in skeletal muscle with inhibition of VEGF-induced angiogenesis at a distant site (the ear). Local delivery of the vectors into the mouse ear also inhibited VEGF-induced ear angiogenesis. Pretreatment of mice with i.m. or intrasplenic injection of rAAV-endostatin or rAAV-3TSR significantly inhibited tumor growth. A single intratumoral injection of each vector also significantly decreased the volume of large established pancreatic tumors. Tumor microvessel density was significantly decreased in each treatment group and was well correlated with tumor volume reduction. Greater antiangiogenic and antitumor effects were achieved when rAAV-3TSR and rAAV-endostatin were combined.
Conclusions: rAAV-mediated 3TSR and endostatin gene therapy showed both localized and systemic therapeutic effects against angiogenesis and tumor growth and may provide promise for patients with pancreatic cancer.
Excision Repair Cross Complementation Group 1 Immunohistochemical Expression Predicts Objective Response and Cancer-Specific Survival in Patients Treated by Cisplatin-Based Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
Authors: Handra-Luca Adriana , Hernandez Juana , Mountzios Giannis , Taranchon Estelle , Lacau-St-Guily Jean , Soria Jean-Charles , Fouret Pierre 
Published: July 2007

Abstract
Purpose: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatin-based induction chemotherapy.
Experimental Design: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 immunohistochemical expression.
Results: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1 at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1 expression. ERCC1 and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value.
Conclusion: Our results suggest that those patients characterized by low ERCC1 expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1 expression.
Rebuilding Human Leukocyte Antigen Class II–Restricted Minor Histocompatibility Antigen Specificity in Recall Antigen-Specific T Cells by Adoptive T Cell Receptor Transfer: Implications for Adoptive Immunotherapy
Authors: Spaapen Robbert , van den Oudenalder Kelly , Ivanov Roman , Bloem Andries , Lokhorst Henk , Mutis Tuna 
Published: July 2007

AbstractPurpose: Donor T cells directed to hematopoietic minor histocompatibility antigens (mHag) are appealing tools for adoptive immunotherapy of hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Toward the development of a convenient strategy for ex vivo generation of human leukocyte antigen (HLA) class II–restricted mHag-specific T cells, we evaluated the feasibility of rebuilding mHag-specific T cell functions in donor-derived recall antigen-specific T cells via T cell receptor (TCR) transfer.Experimental Design: TCR α- and β-chains of an HLA-DPB1*0401–restricted T-cell clone recognizing a multiple myeloma-associated mHag were retrovirally transferred into a tetanus toxoid (TT)–specific clone derived from the original stem cell donor. TCR double-transduced cells were compared with the parent mHag- and TT-specific clones for antigen specificity, cytokine secretion, and cytotoxic activity and were analyzed for their in vitro expansion capacity in a TT- or mHag-specific fashion.Results: mHag-TCR–transduced TT-specific cells displayed both TT and mHag specificity. Similar to the parent cells, they secreted Th-1 cytokines and exerted significant cytotoxic activity against TT-pulsed or mHag+ target cells, including multiple myeloma cells. A 4-week expansion of TCR-transduced cells via the TT-specific TCR had no negative influence on the mHag-specific cytotoxic activity and resulted in 10- to 100-fold better cell yields as compared with mHag-specific expansion.Conclusions: HLA class II–restricted, mHag-specific effector functions can be successfully reconstructed in donor-derived TT-specific T cells via TCR transfer. Effective expansion of these T cells via TT-specific TCRs illustrate the suitability of this strategy for ex vivo expansion and possibly for in vivo TT-specific reboosting of HLA class II–restricted immunotherapeutic T cells.
Up-regulation of Tumor Susceptibility Gene 101 Conveys Poor Prognosis through Suppression of p21 Expression in Ovarian Cancer
Authors: Young Travis W. , Rosen Daniel G. , Mei Fang C. , Li Nan , Liu Jinsong , Wang Xiao-Fan , Cheng Xiaodong 
Published: July 2007

Abstract
Purpose: The function of tumor susceptibility gene 101 (TSG101) in ovarian carcinogenesis is largely unexplored. The aim of this study is to investigate the role of TSG101 in human ovarian cancer development, to examine the expression levels of TSG101 in ovarian carcinomas, and to correlate the results with clinicopathologic variables and survival.
Experimental Design: Human ovarian cancer tissue arrays that contain duplicates of 422 cases of primary ovarian carcinoma were used to probe the expression levels of TSG101 and p21 in epithelial ovarian cancer. In vitro studies in ovarian cancer cells using TSG101-specific small interfering RNA (siRNA) were done to further elucidate the mechanism of TSG101-mediated p21 regulation.
Results: We show that TSG101 is increasingly overexpressed in borderline tumors and low-grade and high-grade carcinomas. Patients with low expression of TSG101 survive longer than those with high expression. Suppressing TSG101 by siRNA in ovarian cancer cells led to growth inhibition, cell cycle arrest, and apoptosis with concurrent increases in p21 mRNA and protein. Consistent with this negative association between TSG101 and p21, expression levels of these two markers are inversely correlated in ovarian cancer.
Conclusions: TSG101 negatively regulates p21 levels, and up-regulation of TSG101 is associated with poor prognosis in ovarian cancer.