bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells
Authors: Lee Young-Ran , Yang In-Ho , Lee Young-Hee , Im Sun-A , Song Sukgil , Li Hong , Han Kun , Kim Kyungjae , Eo Seong Kug , Lee Chong-Kil 
Published: January 2005

AbstractThe main targets for the immunosuppressive calcineurin inhibitors, cyclosporin A (CsA) and tacrolimus, have been considered to be activated T cells, but not antigen-presenting cells. Here we demonstrate that CsA and tacrolimus, but not rapamycin, inhibit major histocompatibility complex (MHC)–restricted antigen presentation in dendritic cells (DCs). Microencapsulated ovalbumin (OVA) was efficiently captured, processed, and presented on both class I MHC molecules (cross-presentation) as well as on class II MHC molecules. Addition of CsA and tacrolimus, but not rapamycin, to cultures of DCs inhibited both the class I processing pathway and the class II processing pathway of exogenous OVA. In addition, CsA and tacrolimus, but not rapamycin, also inhibited the classic class I processing pathway of endogenous OVA. CsA and tacrolimus did not inhibit presentation of exogenously added OVA peptide, SIINFEKL, phagocytic activity of DCs, or the total level of expression of class I MHC (H-2Kb) molecules. CsA and tacrolimus, however, inhibited profoundly the expression of SIINFEKL-H-2Kb complexes in OVA-phagocytized DCs. These results demonstrate clearly that CsA and tacrolimus inhibit intracellular processing events of antigens, and further suggest that the immunosuppressive activity of CsA and tacrolimus is at least in part due to inhibition of antigen processing pathways.
Prognostic Implications of Multiple Lymphatic Basin Drainage in Patients With Truncal Melanoma
Authors: Jimenez Ramon E. , Panageas Katherine , Busam Klaus J. , Brady Mary S. 
Published: January 2005

PurposeLymphatic drainage to multiple basins (MLBD) is frequently observed in patients with truncal melanoma undergoing sentinel lymph node (SLN) mapping. Recently published data suggest that patients with MLBD are at increased risk of nodal metastases compared with those with single lymphatic basin drainage (SLBD). We studied the impact of MLBD on SLN positivity and survival.Patients and MethodsWe identified 266 patients with truncal melanoma undergoing SLN mapping and biopsy from 1995 to 2001. MLBD was defined as lymphoscintigraphic and intraoperative identification of an SLN in more than one nodal basin. Clinical and pathologic variables were recorded and analyzed for their impact on survival.ResultsMLBD occurred in 76 patients (29%), and SLBD occurred in 190 patients (71%). Clinical and pathologic variables were similar between the two groups, although there were more males in the MLBD group (78% v 64%; P = .034). Patients with MLBD did not have higher risk for positive SLNs compared with those with SLBD (22% v 21%, respectively). Five-year survival for patients with MLBD was less favorable than that of patients with SLBD (68% v 78%, respectively; log-rank P = .04). Multivariate analysis revealed that increasing Breslow thickness (P < .001), SLN metastasis (P < .001), and MLBD (P = .04) were independent predictors of poor overall and relapse-free survival. The negative prognostic implication of MLBD remained significant when only patients with negative SLNs were analyzed (relative risk, 2.7; P = .03).ConclusionMLBD in patients with truncal melanoma undergoing SLN mapping is associated with a less favorable survival compared with patients with SLBD, independent of SLN status.
Ewing Sarcomas With p53 Mutation or p16/p14ARF Homozygous Deletion: A Highly Lethal Subset Associated With Poor Chemoresponse
Authors: Huang Hsuan-Ying , Illei Peter B. , Zhao Zhiquan , Mazumdar Madhu , Huvos Andrew G. , Healey John H. , Wexler Leonard H. , Gorlick Richard , Meyers Paul , Ladanyi Marc 
Published: January 2005

Purpose EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. Patients and Methods We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively. Results Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases. Conclusion Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.
Docetaxel and Continuous-Infusion Fluorouracil Versus Epirubicin, Cisplatin, and Fluorouracil for Advanced Gastric Adenocarcinoma: A Randomized Phase II Study
Authors: Thuss-Patience Peter C. , Kretzschmar Albrecht , Repp Michael , Kingreen Dorothea , Hennesser Dirk , Micheel Simone , Pink Daniel , Scholz Christian , Dörken Bernd , Reichardt Peter 
Published: January 2005

Purpose A combination of docetaxel and fluorouracil (DF) was evaluated in an outpatient setting and compared with epirubicin, cisplatin, and fluorouracil (ECF), which served as an internal control arm to avoid selection bias. Patients and Methods Patients with metastatic or locally advanced gastric adenocarcinoma without prior chemotherapy were randomly assigned to receive either ECF (epirubicin 50 mg/m2 day 1, cisplatin 60 mg/m2 day 1, and fluorouracil 200 mg/m2 days 1 through 21, every 3 weeks) or DF (docetaxel 75 mg/m2 day 1, and fluorouracil 200 mg/m2 days 1 through 21, every 3 weeks). Results Ninety patients were randomly assigned. Toxicity was rarely severe. Major toxic effects included diarrhea, stomatitis, and leukopenia in the DF arm and nausea, vomiting, and leukopenia in the ECF arm. Forty-three of 45 patients in each arm were assessable. In the DF arm, two patients (4.4%, intent to treat) experienced a confirmed complete tumor remission as best response, and 15 patients (33.3%) experienced a confirmed partial remission (overall response rate [ORR], 37.8%; 95% CI, 25.9% to 51.9%). Two patients (4.4%) in the ECF arm showed confirmed complete remission, and 14 (31.1%) showed confirmed partial remission (ORR, 35.6%; 95% CI, 24.8% to 48.7%). For the DF and ECF arms, the median survival was 9.5 and 9.7 months, and the median time to tumor progression 5.5 and 5.3 months, respectively. Conclusion DF can be safely given in an ambulant setting. Compared with ECF, the dual combination of DF shows promising efficacy and may be an alternative treatment option that avoids cisplatin.
Long-Term Health-Related Quality of Life, Growth, and Spiritual Well-Being After Hematopoietic Stem-Cell Transplantation
Authors: Andrykowski Michael A. , Bishop Michelle M. , Hahn Elizabeth A. , Cella David F. , Beaumont Jennifer L. , Brady Marianne J. , Horowitz Mary M. , Sobocinski Kathleen A. , Rizzo J. Douglas , Wingard John R. 
Published: January 2005

PurposeTo examine health-related quality of life (HRQOL) and growth, and spiritual well-being in adult survivors of hematopoietic stem-cell transplantation (HSCT) for a malignant disease.MethodsHSCT survivors (n = 662) were recruited through the International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry and were drawn from 40 transplantation centers. HSCT survivors completed a telephone interview and a set of questionnaires a mean of 7.0 years post-HSCT (range, 1.8 to 22.6 years). Study measures included a variety of standardized measures of HRQOL and growth and spiritual well-being. An age- and sex-matched healthy comparison (HC) group (n = 158) was recruited using a peer nomination method. The HC group completed a parallel telephone interview and set of questionnaires.ResultsMultivariate analysis of variance analyses found the HSCT survivor group reported poorer status relative to the HC group for all HRQOL outcome clusters including physical health, physical functioning, social functioning, psychological adjustment, and dyadic adjustment. In contrast, the HSCT survivor group reported more psychological and interpersonal growth. Mean effect size for the 24 outcome indices examined was 0.36 standard deviations, an effect size often considered clinically meaningful or important. The largest group differences were found for measures of general health, physical function and well-being, depression, cognitive function, and fatigue.ConclusionThe experience of HSCT for a malignant disease has a wide-ranging, longstanding, and profound impact on adult recipients. Relative to healthy controls, HSCT survivors reported poorer physical, psychological, and social functioning but, conversely, more psychological and interpersonal growth, differences that appeared to persist many years after HSCT.
Osteosarcoma Relapse After Combined Modality Therapy: An Analysis of Unselected Patients in the Cooperative Osteosarcoma Study Group (COSS)
Authors: Kempf-Bielack Beate , Bielack Stefan S. , Jürgens Heribert , Branscheid Detlev , Berdel Wolfgang E. , Exner G. Ulrich , Göbel Ulrich , Helmke Knut , Jundt Gernot , Kabisch Hartmut , Kevric Mathias , Klingebiel Thomas , Kotz Rainer , Maas Rainer , Schwarz Rudolf , Semik Michael , Treuner Jörn , Zoubek Andreas , Winkler Kurt 
Published: January 2005

Purpose To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. Patients and Methods Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). Results After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. Conclusion Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.
Intensive Systemic Chemotherapy Combined With Surgery for Metastatic Colorectal Cancer: Results of a Phase II Study
Authors: Taïeb Julien , Artru Pascal , Paye François , Louvet Christophe , Perez Nathalie , André Thierry , Gayet Brice , Hebbar Mohamed , Goebel Frédérique Maindrault , Tournigand Christophe , Parc Rolland , de Gramont Aimery 
Published: January 2005

Purpose To evaluate the efficacy and tolerability of the metastatic irinotecan plus oxaliplatin (MIROX) strategy (adjuvant FOLFOX-7 followed by FOLFIRI), in patients with resectable metastatic colorectal cancer. Patients and Methods Forty-seven patients with resectable metastases of colorectal cancer were prospectively enrolled onto this study. Treatment consisted of six cycles of leucovorin 400 mg/m2, oxaliplatin 130 mg/m2 in a 120-minute infusion, and fluorouracil (FU) 2,400 mg/m2 in a 46-hour infusion, every 2 weeks (FOLFOX-7), followed by six cycles of leucovorin 400 mg/m2, irinotecan 180 mg/m2 in a 90-minute infusion, bolus FU 400 mg/m2, and FU 2,400 mg/m2 as a 46-hour infusion, every 2 weeks (FOLFIRI). Surgery was performed before chemotherapy in 25 patients and after six cycles of FOLFOX-7 in 22 patients (six cycles of FOLFIRI were administered after surgery). Results All but one of the patients underwent curative surgery. Two patients refused postoperative chemotherapy. Tolerability was generally good. The main toxicities were grade 3 to 4 neutropenia (13%) and thrombocytopenia (11%); no febrile neutropenia or bleeding occurred, and there were no deaths caused by toxicity. Two pathologically confirmed complete responses and 15 partial responses were obtained with FOLFOX-7 in the 22 patients who received this regimen before surgery (overall response rate, 77%; 95% CI, 68 to 86). The median disease-free survival time was 21 months; the median overall survival has not yet been reached. The 2-year overall and disease-free survival rates were 89% and 47%, respectively. Conclusion The MIROX strategy is feasible and well tolerated by patients with resectable metastatic colorectal cancer. Progression-free and overall survival rates are promising, with a median of 38 months of follow-up. This strategy currently is being compared with the leucovorin and FU regimen in a phase III trial.
Racial Differences in Surgical Evaluation, Treatment, and Outcome of Locoregional Esophageal Cancer: A Population-Based Analysis of Elderly Patients
Authors: Steyerberg Ewout W. , Earle Craig C. , Neville Bridget A. , Weeks Jane C. 
Published: January 2005

Purpose We investigated racial disparities in access to surgical evaluation, receipt of surgery, and survival among elderly patients with locoregional esophageal cancer. Methods We selected 2,946 white patients and 367 black patients who were older than 65 years and had clinically locoregional esophageal cancer in the Surveillance, Epidemiology, and End Results (SEER) registry (1991 to 1999). Treatment and outcome data were obtained from the linked SEER-Medicare databases. We used logistic regression analysis to estimate odds ratios (ORs) for being seen by a surgeon and for undergoing surgery. Cox proportional hazards analyses were performed to estimate hazard ratios (HRs) for survival adjusted for medical, nonmedical, and treatment characteristics. Results The rate of surgery for black patients was half that of white patients (25% v 46%; OR, 0.38; P < .001), which was caused by both a lower rate of seeing a surgeon (70% v 78%; OR, 0.66; P < .001) and a lower rate of surgery once seen (35% v 59%; OR, 0.38; P < .001). These racial disparities were only partly explained by differences in patient and cancer characteristics, and not by nonmedical factors, such as socioeconomic status. The 2-year survival rate was lower for black patients (18% v 25%; HR, 1.18; P = .004), but this racial difference disappeared when corrected for treatment received (adjusted HR, 1.02; P = .80). Conclusion Underuse of potentially curative surgery is an important potential explanation for the poorer survival of black patients with locoregional esophageal cancer. Barriers to surgical evaluation and treatment need to be reduced, whether related to patient or healthcare system factors.
Polymorphisms in FcγRIIIA (CD16) Receptor Expression Are Associated With Clinical Response to Rituximab in Waldenström’s Macroglobulinemia
Authors: Treon Steven P. , Hansen Mark , Branagan Andrew R. , Verselis Sigitas , Emmanouilides Christos , Kimby Eva , Frankel Stanley R. , Touroutoglou Nikolaos , Turnbull Barry , Anderson Kenneth C. , Maloney David G. , Fox Edward A. 
Published: January 2005

PurposeRituximab is an important therapeutic for Waldenström’s macroglobulinemia (WM). Polymorphisms in FcγRIIIA (CD16) receptor expression modulate human immunoglobulin G1 binding and antibody-dependent cell-mediated cytotoxicity, and may therefore influence responses to rituximab.Patients and MethodsSequence analysis of the entire coding region of FcγRIIIA was undertaken in 58 patients with WM whose outcomes after rituximab were known.ResultsVariations in five codons of FcγRIIIA were identified. Two were commonly observed (FcγRIIIA-48 and FcγRIIIA-158) and predicted for amino acid polymorphisms at FcγRIIIA-48: leucine/leucine (L/L), leucine/arginine (L/R), and leucine/histidine (L/H). Polymorphisms at FcγRIIIA-158 were phenylalanine/phenylalanine (F/F), phenylalanine/valine (F/V), and valine/valine (V/V). A clear linkage between these polymorphisms was detected and all patients with FcγRIIIA-158F/F were always FcγRIIIA-48L/L, and patients with either FcγRIIIA-L/R or -L/H always expressed at least one valine at FcγRIIIA-158 (P ≤ .001). The response trend was higher for patients with FcγRIIIA-48L/H (38.5%) versus -48L/R (25.0%) and LL (22.0%), and was significantly higher for patients with FcγRIIIA-158V/V (40.0%) and -V/F (35%) versus -158F/F (9.0%; P = .030). Responses for patients with FcγRIIIA-48L/L were higher when at least one valine was present at FcγRIIIA-158 (P = .057), thereby supporting a primary role for FcγRIIIA-158 polymorphisms in predicting rituximab responses. With a median follow-up of 13 months, no significant differences in the median time to progression and progression-free survival were observed when patients were grouped according to their FcγRIIIA-48 and -158 polymorphisms.ConclusionThe results of these studies therefore support a predictive role for FcγRIIIA-158 polymorphisms and responses to rituximab in WM.
Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial
Authors: Schmid Peter , Schippinger Walter , Nitsch Thorsten , Huebner Gerdt , Heilmann Volker , Schultze Wolfgang , Hausmaninger Hubert , Wischnewsky Manfred , Possinger Kurt 
Published: January 2005

Purpose The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer. Patients and Methods Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates. Results A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity. Conclusion This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.
Imatinib Mesylate in Patients With Adenoid Cystic Cancers of the Salivary Glands Expressing c-kit: A Princess Margaret Hospital Phase II Consortium Study
Authors: Hotte Sébastien J. , Winquist Eric W. , Lamont Elizabeth , MacKenzie Mary , Vokes Everett , Chen Eric X. , Brown Shirley , Pond Gregory R. , Murgo Anthony , Siu Lillian L. 
Published: January 2005

Purpose This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. Patients and Methods In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks. Results Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles. Conclusion Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients.