bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Rates After Year 2000 Significantly Decrease in Children With Perinatal HIV Infection: A Study by the Italian Register for HIV Infection in Children
Authors: Chiappini Elena , Galli Luisa , Tovo Pier-Angelo , Gabiano Clara , Lisi Catiuscia , Giaquinto Carlo , Rampon Osvalda , Gattinara Guido Castelli , De Marco Giulio , Osimani Patrizia , Manzionna Mariano , Miniaci Angela , Pintor Carlo , Rosso Raffaella , Esposito Susanna , Viganò Alessandra , Dodi Icilio , Maccabruni Anna , Fundarò Carlo , de Martino Maurizio 
Published: December 2006

Purpose To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. Patients and Methods An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. Results Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). Conclusion Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.
Pharmacokinetics of Gemcitabine in Japanese Cancer Patients: The Impact of a Cytidine Deaminase Polymorphism
Authors: Sugiyama Emiko , Kaniwa Nahoko , Kim Su-Ryang , Kikura-Hanajiri Ruri , Hasegawa Ryuichi , Maekawa Keiko , Saito Yoshiro , Ozawa Shogo , Sawada Jun-ichi , Kamatani Naoyuki , Furuse Junji , Ishii Hiroshi , Yoshida Teruhiko , Ueno Hideki , Okusaka Takuji , Saijo Nagahiro 
Published: December 2006

Purpose Gemcitabine is rapidly metabolized to its inactive metabolite, 2′,2′-difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported that a patient with homozygous 208A alleles of CDA showed severe adverse reactions with an increase in gemcitabine plasma level. This study extended the investigation of the effects of CDA genetic polymorphisms on gemcitabine pharmacokinetics and toxicities. Patients and Methods Genotyping of CDA was performed by a direct sequencing of DNA obtained from the peripheral blood of Japanese gemcitabine-naïve cancer patients (n = 256). The patients recruited to the association study received a 30-minute intravenous infusion of gemcitabine at a dose of either 800 or 1,000 mg/m2, and eight blood samples were periodically collected (n = 250). Plasma levels of gemcitabine and dFdU were measured by high-performance liquid chromatography. Plasma CDA activities toward cytidine and gemcitabine were also measured (n = 121). Results Twenty-six genetic variations, including 14 novel ones and two known nonsynonymous single nucleotide polymorphisms (SNPs), were detected. Haplotypes harboring the nonsynonymous SNPs 79A>C (Lys27Gln) and 208G>A (Ala70Thr) were designated *2 and *3, respectively. The allelic frequencies of the two SNPs were 0.207 and 0.037, respectively. Pharmacokinetic parameters of gemcitabine and plasma CDA activities significantly depended on the number of haplotype *3. Haplotype *3 was also associated with increased incidences of grade 3 or higher neutropenia in the patients who were coadministered fluorouracil, cisplatin, or carboplatin. Haplotype *2 showed no significant effect on gemcitabine pharmacokinetics. Conclusion Haplotype *3 harboring a nonsynonymous SNP, 208G>A (Ala70Thr), decreased clearance of gemcitabine, and increased incidences of neutropenia when patients were coadministered platinum-containing drugs or fluorouracil.
Comparison of Intensive Chemotherapy, Allogeneic, or Autologous Stem-Cell Transplantation As Postremission Treatment for Children With Very High Risk Acute Lymphoblastic Leukemia: PETHEMA ALL-93 Trial
Authors: Ribera Jose-Maria , Ortega Juan-José , Oriol Albert , Bastida Pilar , Calvo Carlota , Pérez-Hurtado José-María , González-Valentín María-Elvira , Martín-Reina Victoria , Molinés Antonio , Ortega-Rivas Fernando , Moreno Maria-José , Rivas Concepción , Egurbide Izaskun , Heras Inmaculada , Poderós Concepción , Martínez-Revuelta Eva , Guinea José-Maria , del Potro Eloy , Deben Guillermo 
Published: December 2006

Purpose The optimal postremission therapy for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is not well established. This randomized trial compared three options of postremission therapy: chemotherapy and allogeneic or autologous stem-cell transplantation (SCT). Patients and Methods All 106 VHR-ALL patients received induction with five drugs followed by intensification with three cycles of chemotherapy. Patients in complete remission (CR) with an HLA-identical family donor were assigned to allogeneic SCT (n = 24) and the remaining were randomly assigned to autologous SCT (n = 38) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n = 38). Results Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5-year disease-free survival (DFS) and overall survival (OS) probabilities were 45% (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups were comparable in the main pretreatment ALL characteristics. Intention-to-treat analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27% to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI, 43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS: 44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v 57%; 95% CI, 43% to 73%). No differences were found within the different subgroups of ALL and neither were differences observed when the analysis was made by treatment actually performed. Conclusion This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in children with VHR-ALL.
Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide in Previously Treated Germ Cell Tumors
Authors: Kondagunta G. Varuni , Bacik Jennifer , Sheinfeld Joel , Bajorin Dean , Bains Manjit , Reich Lillian , Deluca John , Budnick Amy , Ishill Nicole , Mazumdar Madhu , Bosl George J. , Motzer Robert J. 
Published: December 2006

Purpose To evaluate the optimal dose of carboplatin as well as the efficacy and tolerability of sequential, dose-intense chemotherapy with paclitaxel and ifosfamide followed by carboplatin and etoposide (TICE) plus peripheral-blood stem-cell (PBSC) support in patients with germ cell tumors (GCT) who are likely to experience treatment failure with conventional-dose salvage treatment. This prospective trial followed a similarly designed report of TICE, which used a different means of carboplatin dosing. Patients and Methods The 48 patients entered onto this trial had progressive GCT and unfavorable prognostic features after chemotherapy. Two cycles of paclitaxel plus ifosfamide were administered with leukapheresis, followed by three cycles of carboplatin plus etoposide with reinfusion of PBSC. Results Twenty-three (49%) of 47 assessable patients achieved a complete response (CR) to chemotherapy. An additional three patients (6%) achieved a CR to chemotherapy and surgery. The CR rate was 55%. Six patients experienced relapse, but 24 patients (51%) are alive and free of disease at a median follow-up time of 40 months. Four patients who experienced relapse or achieved an incomplete response were rendered disease free by salvage surgical resection. When combined with results of the prior trial of similar design, TICE chemotherapy yielded an overall CR of 56% (n = 84), with 50% of patients alive with no evidence of disease. Conclusion TICE is an effective and tolerable dose-intense treatment for patients with previously treated metastatic GCT who have a poor predicted outcome to conventional-dose salvage chemotherapy.
Screening for Coronary Artery Disease After Mediastinal Irradiation for Hodgkin's Disease
Authors: Heidenreich Paul A. , Schnittger Ingela , Strauss H. William , Vagelos Randall H. , Lee Byron K. , Mariscal Carol S. , Tate David J. , Horning Sandra J. , Hoppe Richard T. , Hancock Steven L. 
Published: December 2006

Purpose Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease. Patients and Methods We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses ≥ 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician. Results Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis ≥ 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal). Conclusion Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.
Volume-Based Referral for Cancer Surgery: Informing the Debate
Authors: Hollenbeck Brent K. , Dunn Rodney L. , Miller David C. , Daignault Stephanie , Taub David A. , Wei John T. 
Published: December 2006

Purpose Mounting evidence suggests a relationship between hospital volume and outcomes after major cancer surgery; however, the absolute benefits of volume-based referral on a national basis are unclear. Patients and Methods Data from the Nationwide Inpatient Sample were used to measure the likelihood of operative mortality and a prolonged length of stay (LOS) after six cancer surgeries (prostatectomy, cystectomy, esophagectomy, pancreatectomy, pneumonectomy, and liver resection) between 1993 and 2003. Using sampling weights, the adjusted likelihood of the outcomes was used to calculate the number of lives saved (or prolonged LOS avoided) in the United States. Results The magnitude of the volume–operative mortality effect varied from an adjusted odds ratio (OR) of 1.3 (95% CI, 0.8 to 2.3) for cystectomy to 4.9 (95% CI, 2.4 to 10.1) for pancreatectomy. After accounting for varying rates of procedure utilization, the lives saved per 100 surgeries regionalized ranged from 0.2 (95% CI, 0.12 to 0.24 lives saved) for prostatectomy to 9.2 (95% CI, 6.7 to 10.4 lives saved) for pancreatectomy. The volume–prolonged LOS effect varied from an adjusted OR of 0.9 (95% CI, 0.5 to 1.6) for liver resection to 4.8 (95% CI, 3.5 to 6.7) for prostatectomy. After accounting for procedure use, the number of prolonged hospitalizations avoided ranged from −1.7 (95% CI, −11.3 to 3.6 hospitalizations) to 14.3 (95% CI, 12.9 to 15.4 hospitalizations) per 100 surgeries regionalized for liver resection and prostatectomy, respectively. Conclusion For patients undergoing major cancer surgery, the benefits of volume-based referral depend on the interplay between procedure utilization, the magnitude of effect, and the outcome chosen.
Incidence of Venous Thromboembolism and the Impact on Survival in Breast Cancer Patients
Authors: Chew Helen K. , Wun Theodore , Harvey Danielle J. , Zhou Hong , White Richard H. 
Published: December 2006

Purpose The incidence of venous thromboembolism (VTE) and the risk factors associated with development of VTE have not been reported in a large population-based study of breast cancer patients. Patients and Methods The California Cancer Registry was merged with the Patient Discharge Data Set, and the number of VTE events determined among patients diagnosed between 1993 and 1999. Results Among 108,255 patients with breast cancer, the 2-year cumulative VTE incidence was 1.2%, with a rate of 1.2 and 0.6 events/100 patient-years during the first and second half-year, respectively. The 1-year incidence of VTE was significantly increased compared with the general population (standardized incidence ratio of VTE, 4.2; 95% CI, 3.9 to 4.4). In a multivariate model, significant predictors of developing VTE within 2 years were: age (hazard ratio [HR], 2.0 if > 75 years v < 45; 95% CI, 1.6 to 2.6), the number of chronic medical comorbidities (HR, 2.9 if 3 v 0; 95% CI, 2.4 to 3.5), and advancing cancer stage (HR, 6.3; 95% CI, 5.3 to 7.5 for metastatic v local disease). In multivariate models, VTE was a significant predictor of decreased 2-year survival (HR, 2.3; 95% CI, 2.1 to 2.6) and when stratified by initial cancer stage, the effect was highest in patients with localized (HR, 5.1; 95% CI, 3.6 to 7.1) or regional stage (HR, 3.5; 95% CI, 2.5 to 4.8) cancer compared with patients with metastatic disease (HR, 1.9; 95% CI, 1.5 to 2.4). Conclusion Approximately 1% of breast cancer patients developed VTE within 2 years, with the highest incidence in the first 6 months after diagnosis. Metastatic disease and comorbidities were the strongest predictors. The diagnosis of VTE was associated with a higher risk of death within 2 years.
Phase III Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage III Colon Cancer: A Planned Safety Analysis in 1,864 Patients
Authors: Schmoll Hans-Joachim , Cartwright Thomas , Tabernero Josep , Nowacki Marek P. , Figer Arie , Maroun Jean , Price Timothy , Lim Robert , Van Cutsem Eric , Park Young-Suk , McKendrick Joseph , Topham Claire , Soler-Gonzalez Gemma , de Braud Filipo , Hill Mark , Sirzén Florin , Haller Daniel G. 
Published: December 2006

Purpose To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer. Patients and Methods Patients with stage III colon carcinoma were randomly assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine; 3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY) regimen for a similar length of time. A total of 1,886 patients were randomly assigned. Results The safety population comprised 1,864 patients, of whom 938 received XELOX and 926 received FU/LV. Most treatment-related adverse events (AEs) occurred at similar rates in both treatment arms. However, patients receiving XELOX experienced less all-grade diarrhea, alopecia, and more neurosensory toxicity, vomiting, and hand-foot syndrome than those patients receiving FU/LV. Compared with Mayo, XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE. Compared with RP, XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE. As expected grade 3/4 neurosensory toxicity and grade 3 hand-foot syndrome were higher with XELOX. Treatment-related mortality within 28 days from the last study dose was 0.6% in the XELOX group and 0.6% in the FU/LV group. Conclusion XELOX has a manageable tolerability profile in the adjuvant setting. Efficacy data will be available within the next 24 months.
Antithyroid Drugs Inhibit Thyroid Hormone Receptor-Mediated Transcription
Authors: Moriyama Kenji , Tagami Tetsuya , Usui Takeshi , Naruse Mitsuhide , Nambu Takuo , Hataya Yuji , Kanamoto Naotetsu , Li Yu-shu , Yasoda Akihiro , Arai Hiroshi , Nakao Kazuwa 
Published: December 2006

AbstractContext: Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves’ disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5′-deiodination of T4 in peripheral tissues. ATDs may also interfere with T3 binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T3 mediated by TRs has not been studied.Objective: The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T3 and TRs in vitro.Methods: Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined.Results: In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T3 in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T3. In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T3. Finally, MMI decreased the GH release that was stimulated by T3.Conclusions: ATDs inhibit T3 action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T3 action at the transcriptional level.
Follicular Phase Dynamics with Combined Aromatase Inhibitor and Follicle Stimulating Hormone Treatment
Authors: Bedaiwy Mohamed A. , Mousa Noha A. , Esfandiari Navid , Forman Rachel , Casper Robert F. 
Published: December 2006

Abstract
Objective: The objective of this study was to evaluate follicular phase parameters during ovarian stimulation with FSH alone or with the aromatase inhibitor letrozole.
Methods: Two groups of women undergoing intrauterine insemination (IUI): group I (389 patients; mean age 35 ± 4.3 yr) underwent 630 IUI cycles stimulated with letrozole and FSH; and group II (134 patients; mean age 36.0 ± 4.6 yr) underwent 166 IUI cycles stimulated with FSH only. Each group was stratified into ovulatory and anovulatory cycles. Patients were monitored by ultrasound for folliculometry and blood sampling for hormonal assay on d 3, 7, 9, or 10 of the cycle, and on the day of human chorionic gonadotropin administration.
Results: Group I had a significantly lower follicular count greater than 10 mm on d 7, greater than 12 mm on d 9 or 10, and greater than 15 mm on the day of human chorionic gonadotropin administration compared to group II (P = 0.006, &lt;0.001, and &lt;0.001, respectively). After stratifying patients by diagnosis, this relationship was maintained only for patients with ovulatory infertility (P = 0.003, &lt;0.001, and &lt;0.001, respectively). Serum estradiol (E2) was significantly lower in the group I ovulatory and anovulatory at the last three monitoring visits (P &lt; 0.001). However, the difference in E2 levels decreased in the preovulatory period with similar E2 levels per mature follicle. No premature preovulatory progesterone rise was observed in either group. However, significantly lower progesterone levels were observed in the second half of the follicular phase in group I (P = 0.02 and &lt;0.001). Endometrial thickness was significantly lower in group I at the second and third visits (P &lt; 0.001, 0.01) but was comparable to group II at the last monitoring visit. Although, the pregnancy rates were similar between the two groups, the multiple pregnancy rate was significantly higher in the FSH-only group (P = 0.039).
Conclusion: The addition of letrozole modifies the follicular, hormonal, and endometrial dynamics of FSH-stimulated cycles with possible positive effects on the overall cycle outcome.
Foxl2 Up-Regulates Aromatase Gene Transcription in a Female-Specific Manner by Binding to the Promoter as Well as Interacting with Ad4 Binding Protein/Steroidogenic Factor 1
Authors: Wang De-Shou , Kobayashi Tohru , Zhou Lin-Yan , Paul-Prasanth Bindhu , Ijiri Shigeho , Sakai Fumie , Okubo Kataaki , Morohashi Ken-ichirou , Nagahama Yoshitaka 
Published: December 2006

AbstractIncreasing evidence suggests the crucial role of estrogen in ovarian differentiation of nonmammalian vertebrates including fish. The present study has investigated the plausible role of Foxl2 in ovarian differentiation through transcriptional regulation of aromatase gene, using monosex fry of tilapia. Foxl2 expression is sexually dimorphic, like Cyp19a1, colocalizing with Cyp19a1 and Ad4BP/SF-1 in the stromal cells and interstitial cells in gonads of normal XX and sex-reversed XY fish, before the occurrence of morphological sex differentiation. Under in vitro conditions, Foxl2 binds to the sequence ACAAATA in the promoter region of the Cyp19a1 gene directly through its forkhead domain and activates the transcription of Cyp19a1 with its C terminus. Foxl2 can also interact through the forkhead domain with the ligand-binding domain of Ad4BP/SF-1 to form a heterodimer and enhance the Ad4BP/SF-1 mediated Cyp19a1 transcription. Disruption of endogenous Foxl2 in XX tilapia by overexpression of its dominant negative mutant (M3) induces varying degrees of testicular development with occasional sex reversal from ovary to testis. Such fish display reduced expression of Cyp19a1 as well as a drop in the serum levels of 17β-estradiol and 11-ketotestosterone. Although the XY fish with wild-type tilapia Foxl2 (tFoxl2) overexpression never exhibited a complete sex reversal, there were significant structural changes, such as tissue degeneration, somatic cell proliferation, and induction of aromatase, with increased serum levels of 17β-estradiol and 11-ketotestosterone. Altogether, these results suggest that Foxl2 plays a decisive role in the ovarian differentiation of the Nile tilapia by regulating aromatase expression and possibly the entire steroidogenic pathway.
Electrical Conductance Measurement of Oligothiophene Molecular Wires Using Nanogap Electrodes Prepared by Electrochemical Plating
Authors: Hatanaka Natsumu , Endo Masaru , Okumura Shigeki , Ie Yutaka , Yamada Ryo , Aso Yoshio , Tanaka Kazuyoshi , Tada Hirokazu 
Published: December 2006

Abstract
Nanogap electrodes were prepared by electroplating. The starting electrodes of gold were patterned by conventional photolithography and lift-off techniques, and the gap separation was reduced by depositing gold in electroplating solution. Careful control of deposition conditions by monitoring the current through the electrodes enabled us to obtain the electrodes with the separation of less than 10 nm. Electrical conductunce of newly designed oligothiophene wires was measuerd with the nanogap electrodes prepared.