bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC)
Authors: Chen Jianping , Hong Kunxue , Jia Mingming , Liu Hongwei , Zhang Yuanzhi , Liu Sha , Zhang Xiaoqing , Zhao Hongjing , Peng Hong , Ma Pengfei , Xing Hui , Ruan Yuhua , Williams Katie L , Yu Xu G , Altfeld Marcus , Walker Bruce D , Shao Yiming 
Published: August 2007

Abstract

Background
The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC), which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP) covering the whole concensus clades B and C proteome.

Results
The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413) of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574) can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load.

Conclusion
This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were demonstrated with clade B infected populations. The immunodominant regions identified in this population can facilitate future HIV-1 vaccine development in China.
Synchronously diagnosed lymph nodal collision tumor of malignant melanoma and chonic lymphocytic leukemia/small lymphocytic lymphoma: case report
Authors: El Demellawy Dina , Ross Catherine , Sur Monalisa , Alowami Salem 
Published: August 2007

Abstract
Synchronous composite tumors have been described but are uncommon. Moreover, simultaneous occurrence of synchronous tumors in the same tissue or organ is even less common. We report a case of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and malignant melanoma (MM) occurring synchronously in the same lymph node. Several cases of an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of which included CLL and MM, occurring in the same patient often CLL after MM. The risk of having CLL after MM has been reported to be increased. Various genetic and environmental etiologies have been postulated, but have as yet not been proven. To our knowledge this is the first time that synchronous occurrence of these two malignant processes in the same tissue is described. In this case it is important that the melanoma was recognized in the excised lymph node, as this finding had much more critical treatment and long term survival consequences.
Verifying 4D gated radiotherapy using time-integrated electronic portal imaging: a phantom and clinical study
Authors: van Sörnsen de Koste John R , Cuijpers Johan P , de Geest Frank GM , Lagerwaard Frank J , Slotman Ben J , Senan Suresh 
Published: August 2007

Abstract
Background
Respiration-gated radiotherapy (RGRT) can decrease treatment toxicity by allowing for smaller treatment volumes for mobile tumors. RGRT is commonly performed using external surrogates of tumor motion. We describe the use of time-integrated electronic portal imaging (TI-EPI) to verify the position of internal structures during RGRT delivery

Methods
TI-EPI portals were generated by continuously collecting exit dose data (aSi500 EPID, Portal vision, Varian Medical Systems) when a respiratory motion phantom was irradiated during expiration, inspiration and free breathing phases. RGRT was delivered using the Varian RPM system, and grey value profile plots over a fixed trajectory were used to study object positions. Time-related positional information was derived by subtracting grey values from TI-EPI portals sharing the pixel matrix. TI-EPI portals were also collected in 2 patients undergoing RPM-triggered RGRT for a lung and hepatic tumor (with fiducial markers), and corresponding planning 4-dimensional CT (4DCT) scans were analyzed for motion amplitude.

Results
Integral grey values of phantom TI-EPI portals correlated well with mean object position in all respiratory phases. Cranio-caudal motion of internal structures ranged from 17.5–20.0 mm on planning 4DCT scans. TI-EPI of bronchial images reproduced with a mean value of 5.3 mm (1 SD 3.0 mm) located cranial to planned position. Mean hepatic fiducial markers reproduced with 3.2 mm (SD 2.2 mm) caudal to planned position. After bony alignment to exclude set-up errors, mean displacement in the two structures was 2.8 mm and 1.4 mm, respectively, and corresponding reproducibility in anatomy improved to 1.6 mm (1 SD).

Conclusion
TI-EPI appears to be a promising method for verifying delivery of RGRT. The RPM system was a good indirect surrogate of internal anatomy, but use of TI-EPI allowed for a direct link between anatomy and breathing patterns.
Phase I/II Trial of Temsirolimus Combined With Interferon Alfa for Advanced Renal Cell Carcinoma
Authors: Motzer Robert J. , Hudes Gary R. , Curti Brendan D. , McDermott David F. , Escudier Bernard J. , Negrier Sylvie , Duclos Brigitte , Moore Laurence , O'Toole Timothy , Boni Joseph P. , Dutcher Janice P. 
Published: August 2007

Purpose Temsirolimus, an inhibitor of the mammalian target of rapamycin, has single-agent activity against advanced renal cell carcinoma (RCC). A recommended dose and safety profile for the combination of temsirolimus and interferon alfa (IFN) were determined in patients with advanced RCC. Patients and Methods Patients were enrolled onto a multicenter, ascending-dose study of temsirolimus (5, 10, 15, 20, or 25 mg) administered intravenously once a week combined with IFN (6 or 9 million units [MU]) administered subcutaneously three times per week. An expanded cohort was treated at the recommended dose to obtain additional safety and efficacy information. Results Seventy-one patients were entered to receive one of six dose levels. The recommended dose was temsirolimus 15 mg/IFN 6 MU based on dose-limiting toxicities of stomatitis, fatigue, and nausea/vomiting, which were observed at higher doses of temsirolimus and IFN. The most frequent grade 3 or 4 toxicities occurring in any cycle included leukopenia, hypophosphatemia, asthenia, anemia, and hypertriglyceridemia for all patients and those who received the recommended dose. Among patients who received the recommended dose (n = 39), 8% achieved partial response and 36% had stable disease for at least 24 weeks. Median progression-free survival for all patients in the study was 9.1 months. Conclusion The combination of temsirolimus and IFN has an acceptable safety profile and displays antitumor activity in patients with advanced RCC. Temsirolimus 15 mg plus IFN 6 MU is the recommended dose for evaluation in a randomized phase III study.
Prevalence, Clinical Pattern, and Outcome of CNS Involvement in Childhood and Adolescent Non-Hodgkin's Lymphoma Differ by Non-Hodgkin's Lymphoma Subtype: A Berlin-Frankfurt-Münster Group Report
Authors: Salzburg Janina , Burkhardt Birgit , Zimmermann Martin , Wachowski Olga , Woessmann Wilhelm , Oschlies Ilske , Klapper Wolfram , Wacker Hans-Heinrich , Ludwig Wolf-Dieter , Niggli Felix , Mann Georg , Gadner Helmut , Riehm Hansjoerg , Schrappe Martin , Reiter Alfred 
Published: August 2007

Purpose We analyzed the prevalence, clinical pattern, and prognostic impact of CNS involvement in a large cohort of children and adolescents diagnosed with non-Hodgkin's lymphoma (NHL), with special attention to differences according to NHL subtype. Patients and Methods From October 1986 to December 2002, 2,381 patients (median age, 9.37 years; range, 0.2 to 23.8 years; female-to-male ratio, 1:2.7) from Germany, Austria, and Switzerland were registered. A total of 2,086 patients were eligible for the consecutive multicenter protocols NHL–Berlin-Frankfurt-Münster [BFM] -86, NHL-BFM-90, and NHL-BFM-95, and could be evaluated for outcome. Results CNS involvement was diagnosed in 141 (5.9%) of 2,381 patients and was associated with an advanced stage of NHL. The percentage of CNS-positive patients was 8.8% for Burkitt's lymphoma/Burkitt's leukemia (BL/B-ALL), 5.4% for precursor B–lymphoblastic lymphoma (pB-LBL), 3.3% for anaplastic large-cell lymphoma, 3.2% for T-cell–LBL, 2.6% for diffuse large B-cell lymphoma, and 0% for primary mediastinal large B-cell NHL (P < .001). Most CNS-positive patients with pB-LBL, T-LBL, or BL/B-ALL had meningeal disease. The probability of event-free survival (pEFS; ± SE) at 5 years was 85% ± 1% for the 2,086 protocol patients (median follow-up, 6.5 years; range, 0.3 to 17.7 years). For the 112 CNS-positive patients, pEFS was 64% ± 5%, compared with 86% ± 1% for the 1,927 CNS-negative patients (P < .001). Although CNS disease had no impact on pEFS for advanced-stage T-LBL patients, CNS-positive patients with BL/B-ALL had a worse average outcome than CNS-negative patients with stage IV BL/B-ALL (60% ± 5% v 81% ± 3%; P < .001). In multivariate analysis, CNS disease was the strongest predictor for relapse in BL/B-ALL patients with advanced-stage disease. Conclusion Six percent of childhood/adolescent NHL patients were CNS positive. However, the prevalence, pattern, and prognostic impact of CNS involvement differed among NHL subtypes.
Multicenter, Randomized, Phase II Trial of CI-1033, an Irreversible Pan-ERBB Inhibitor, for Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Jänne Pasi A. , von Pawel Joachim , Cohen Roger B. , Crino Lucio , Butts Charles A. , Olson Steven S. , Eiseman Irene A. , Chiappori Alberto A. , Yeap Beow Y. , Lenehan Peter F. , Dasse Kathy , Sheeran Meredith , Bonomi Philip D. 
Published: August 2007

Purpose To evaluate the efficacy of the pan-ERBB inhibitor, CI-1033, in platinum-refractory or recurrent advanced-stage non–small-cell lung cancer (NSCLC). Patients and Methods This open-label, randomized phase II trial evaluated CI-1033 in patients with advanced-stage NSCLC who experienced treatment failure after or were refractory to platinum-based chemotherapy. Three oral CI-1033 doses were evaluated in 21-day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1-year survival rate. Results One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug-related adverse events were rash and diarrhea. The 450-mg arm (14 days on/7 days off) was closed early due to an excessive rate of adverse events. The 1-year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression. Conclusion CI-1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection.
Prostate-Specific Antigen and Pain Surrogacy Analysis in Metastatic Hormone-Refractory Prostate Cancer
Authors: Armstrong Andrew J. , Garrett-Mayer Elizabeth , Ou Yang Yi-Chun , Carducci Michael A. , Tannock Ian , de Wit Ronald , Eisenberger Mario 
Published: August 2007

Purpose It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial. Patients and Methods In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate. Results A ≥ 30% PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95% CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95% CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a ≥ 30% PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival. Conclusion In the TAX327 trial, a PSA decline of ≥ 30% within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.
Nuclear Factor-kB Tumor Expression Predicts Response and Survival in Irinotecan-Refractory Metastatic Colorectal Cancer Treated With Cetuximab-Irinotecan Therapy
Authors: Scartozzi Mario , Bearzi Italo , Pierantoni Chiara , Mandolesi Alessandra , Loupakis Fotios , Zaniboni Alberto , Catalano Vincenzo , Quadri Antonello , Zorzi Fausto , Berardi Rossana , Biscotti Tommasina , Labianca Roberto , Falcone Alfredo , Cascinu Stefano 
Published: August 2007

Purpose NF-kB expression has been shown to be responsible for resistance to antineoplastic agents and it also plays a part in the activation of the epidermal growth factor receptor downstream signaling pathway in colorectal tumors. The aim of our analysis was to investigate a correlation between NF-kB expression, response rate, time to progression, and survival in advanced colorectal cancer patients receiving cetuximab and irinotecan. Patients and Methods We analyzed retrospectively the immunoreactivity for NF-kB in irinotecan-refractory patients receiving cetuximab and irinotecan. Results Seventy-six patients were analyzed. Cetuximab and irinotecan were administered as second-line chemotherapy in 19 patients and after ≥ two lines of chemotherapy in the remaining 57 patients. We observed a partial response (PR) in 16 patients for an overall response rate of 24%. Thirty-two patients (48%) experienced progressive disease; median time to progression (TTP) was 3.6 months and median overall survival was 10.3 months. NF-kB was positive in 46 patients (60%). All main clinical characteristics were well balanced between NF-kB–positive and NF-kB–negative patients. The response rate was 10% (four PRs) versus 48% (12 PRs; P = .0007) in NF-kB–positive and NF-kB–negative tumors, respectively. Median TTP in NF-kB–positive patients was 3 v 6.4 months in the remaining patients (P = .021). Median overall survival was 9.5 v 15.8 months for NF-kB–positive and NF-kB–negative patients, respectively (P = .036) Conclusion The difference in median TTP, overall survival, and response rate seem to confirm that NF-kB may play a crucial role in predicting the efficacy of cetuximab and irinotecan in advanced colorectal tumors.
Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy With Uracil-Tegafur for Adenocarcinoma of the Lung
Authors: Suehisa Hiroshi , Toyooka Shinichi , Hotta Katsuyuki , Uchida Akiko , Soh Junichi , Fujiwara Yoshiro , Matsuo Keitaro , Ouchida Mamoru , Takata Minoru , Kiura Katsuyuki , Date Hiroshi 
Published: August 2007

PurposeAdjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur.Patients and MethodsThe EGFR mutational status of 187 patients with resected lung adenocarcinomas was determined using a polymerase chain reaction–based assay for EGFR exons 19 and 21; the results were then correlated with the effect of adjuvant uracil-tegafur chemotherapy on survival. The antiproliferative effect of fluorouracil (FU) on adenocarcinoma cell lines with EGFR wild-type or mutant type status was examined by measuring the inhibitory concentrations at 50% (IC50s).ResultsAmong the 187 patients, 68 received uracil-tegafur as adjuvant chemotherapy, and 119 were not treated with any chemotherapeutic agents. EGFR mutations were present in 79 patients (43%). Overall, the adjuvant chemotherapy with uracil-tegafur significantly prolonged survival compared with the control group (hazard ratio = 0.38; P = .005). The survival benefit of adjuvant chemotherapy with uracil-tegafur was also examined after stratifying the patients according to EGFR mutation status. Adjuvant chemotherapy significantly prolonged survival among patients with EGFR wild-type tumors (hazard ratio = 0.34; P = .013) but not among patients with EGFR mutant tumors. In an in vitro experiment, the IC50s of EGFR mutant cells to FU were higher than those of wild-type cells, indicating that EGFR wild-type cells are more sensitive to FU than mutant cells.ConclusionEGFR status influenced the effect of adjuvant chemotherapy with uracil-tegafur. Adjuvant chemotherapy could be customized based on EGFR status.
Pleural Effusion in Patients With Chronic Myelogenous Leukemia Treated With Dasatinib After Imatinib Failure
Authors: Quintás-Cardama Alfonso , Kantarjian Hagop , O'Brien Susan , Borthakur Gautham , Bruzzi John , Munden Reginald , Cortes Jorge 
Published: August 2007

Purpose We investigated the risk factors and management of pleural effusion associated with dasatinib therapy for chronic myelogenous leukemia (CML) after failure of imatinib. Patients and Methods We analyzed 138 patients with CML treated with dasatinib from November 2003 to January 2006 in one phase I (n = 50) and four phase II (n = 88) studies for the development of pleural effusion. Results Pleural effusion occurred in 48 patients (35%; grade 3/4 in 23 [17%]), including 29% of those treated in chronic phase (CP), 50% in accelerated phase (AP), and 33% in blast phase (BP). By multivariate analysis, history of cardiac disease, hypertension, and use of a twice-daily schedule (v once daily) were identified as factors associated with development of pleural effusions. Effusions were exudative in 78% of the assessable cases. In some patients, effusions were associated with reversible increments of right ventricular systolic pressure. Management included transient dasatinib interruption in 83%, diuretics in 71%, pulse steroids in 27%, and thoracentesis in 19% of patients. Conclusion Pleural effusions occur during dasatinib therapy, particularly among patients in AP or BP. A twice-daily schedule may result in a higher incidence of pleural effusion. Close monitoring and timely intervention may allow patients to continue therapy and achieve the desired clinical benefit.
Effect of Sample Aliquot Size on the Limit of Detection and Reproducibility of Clinical Assays
Authors: Chen Guorong , Kobayashi Lori , Nazarenko Irina 
Published: August 2007

Abstract
Background: Nucleic acid amplification technologies significantly improved the limit of detection (LOD) for diagnostic assays. The ability of these assays to amplify fewer than 10 target copies of DNA or RNA imposes new requirements on the preparation of clinical samples. We report a statistical method to determine how large of an aliquot is necessary to reproducibly provide a detectable number of cells.
Methods: We determined the success probability (p) based on aliquot size and sample volume. The binomial distribution, based on p and the concentration of cells in sample, was used to calculate the probability of getting no target objects in an aliquot and to determine the minimum number of objects per aliquot necessary to generate a reproducible clinical assay.
Results: The described method was applied to find a minimum aliquot volume required for a set LOD, false-negative rate (FNR), and %CV. For example, to keep FNR &lt;0.01% for 0.5%, 1% and 2% aliquots (minimum 2000, 1000, and 500 cells per sample) are required. Comparison between experimental and predicted FNR demonstrated good correlation for the small volume aliquots and/or low concentration of target. When 4 μL of 200 copies/mL of plasmid is amplified, predicted and experimental FNRs are 47.2% and 44.9%.
Conclusion: This probability model is a useful tool to predict the impact of aliquot volume on the LOD and reproducibility of clinical assays. Even for samples for which pathogens are homogeneously distributed, it is theoretically impossible to collect a single pathogen consistently if the concentration of pathogen is below a certain limit.
A Novel Equation to Estimate Glomerular Filtration Rate Using Beta-Trace Protein
Authors: White Christine A , Akbari Ayub , Doucette Steve , Fergusson Dean , Hussain Naser , Dinh Laurent , Filler Guido , Lepage Nathalie , Knoll Greg A 
Published: August 2007

Abstract
Background: Beta-trace protein (BTP) is a low molecular weight glycoprotein that is a more sensitive marker of glomerular filtration rate (GFR) than serum creatinine. The utility of BTP has been limited by the lack of an equation to translate BTP into an estimate of GFR. The objectives of this study were to develop a BTP-based GFR estimation equation.
Methods: We measured BTP and GFR by 99mtechnetium-diethylenetriaminepentaacetic acid in 163 stable adult renal transplant recipients. Stepwise multiple regression models were created to predict GFR corrected for body surface area. The following variables were considered for entry into the model: BTP, urea, sex, albumin, creatinine, age, and race.
Results: BTP alone accounted for 75.6% of variability in GFR. The model that included all the predictor variables had the largest coefficient of determination (R2) at 0.821. The model with only BTP, urea, and sex had only a slightly lower R2 of 0.81 and yielded the following equation: GFR mL · min−1 · (1.73 m2)−1 = 112.1 × BTP−0.662 × Urea−0.280 × (0.88 if female). A 2nd equation (R2 = 0.79) using creatinine instead of urea was also developed: GFR mL · min−1 · (1.73 m2)−1 = 1.678 × BTP−0.758 × creatinine−0.204 × (0.871 if female).
Conclusions: We have shown that BTP can be used in a simple equation to estimate GFR. Further study is needed in other populations to determine accuracy and clinical utility of this equation.