bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen-Regulated Genes Predict Survival in Hormone Receptor–Positive Breast Cancers
Authors: Oh Daniel S. , Troester Melissa A. , Usary Jerry , Hu Zhiyuan , He Xiaping , Fan Cheng , Wu Junyuan , Carey Lisa A. , Perou Charles M. 
Published: February 2006

Purpose The prognosis of a patient with estrogen receptor (ER) and/or progesterone receptor (PR) –positive breast cancer can be highly variable. Therefore, we developed a gene expression–based outcome predictor for ER+ and/or PR+ (ie, luminal) breast cancer patients using biologic differences among these tumors. Materials and Methods The ER+ MCF-7 breast cancer cell line was treated with 17β-estradiol to identify estrogen-regulated genes. These genes were used to develop an outcome predictor on a training set of 65 luminal epithelial primary breast carcinomas. The outcome predictor was then validated on three independent published data sets. Results The estrogen-induced gene set identified in MCF-7 cells was used to hierarchically cluster a 65 tumor training set into two groups, which showed significant differences in survival (P = .0004). Supervised analyses identified 822 genes that optimally defined these two groups, with the poor-prognosis group IIE showing high expression of cell proliferation and antiapoptosis genes. The good prognosis group IE showed high expression of estrogen- and GATA3-regulated genes. Mean expression profiles (ie, centroids) created for each group were applied to ER+ and/or PR+ tumors from three published data sets. For all data sets, Kaplan-Meier survival analyses showed significant differences in relapse-free and overall survival between group IE and IIE tumors. Multivariate Cox analysis of the largest test data set showed that this predictor added significant prognostic information independent of standard clinical predictors and other gene expression–based predictors. Conclusion This study provides new biologic information concerning differences within hormone receptor–positive breast cancers and a means of predicting long-term outcomes in tamoxifen-treated patients.
Multicenter Phase I Study of Repeated Intratumoral Delivery of Adenoviral p53 in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Fujiwara Toshiyoshi , Tanaka Noriaki , Kanazawa Susumu , Ohtani Shoichiro , Saijo Yasuo , Nukiwa Toshihiro , Yoshimura Kunihiko , Sato Tetsuo , Eto Yoshikatsu , Chada Sunil , Nakamura Haruhiko , Kato Harubumi 
Published: February 2006

Purpose To determine the feasibility, safety, humoral immune response, and biologic activity of multiple intratumoral injections of Ad5CMV-p53, and to characterize the pharmacokinetics of Ad5CMV-p53 in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled onto this phase I trial. Nine patients received escalating dose levels of Ad5CMV-p53 (1 × 109 to 1 × 1011 plaque-forming units) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Ad5CMV-p53 in combination with intravenous administration of cisplatin (80 mg/m2). Patients were monitored for toxicity, vector distribution, antibody formation, and tumor response. Results Fifteen patients received a total of 63 intratumoral injections of Ad5CMV-p53 without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite of the presence of neutralizing antiadenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting at least 9 months, and two patients had progressive disease. Conclusion Multiple courses of intratumoral Ad5CMV-p53 injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.
Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival
Authors: Petrilli A. Sérgio , de Camargo Beatriz , Filho Vicente Odone , Bruniera Paula , Brunetto Algemir L. , Jesus-Garcia Reynaldo , Camargo Olavo P. , Pena Walter , Péricles Pedro , Davi Alexandre , Prospero José D. , Alves Maria Teresa S. , Oliveira Claudia R. , Macedo Carla R.D. , Mendes Wellington L. , Almeida Maria Teresa A. , Borsato Maria L. , dos Santos Telma M. , Ortega Jorge , Consentino Elio 
Published: February 2006

Purpose To evaluate the impact of chemotherapy and surgery on the outcome of osteosarcoma (OS) of the extremities and to identify prognostic factors in Brazilian patients. Patients and Methods A total of 225 patients with metastatic and nonmetastatic OS of the extremities were enrolled and assessed in two consecutive studies designed and implemented by the Brazilian Osteosarcoma Treatment Group. Results The 5-year survival and event-free survival rates for the 209 assessable patients were 50.1% and 39%, respectively; for the 178 patients with nonmetastatic disease at diagnosis, the rates were 60.5% and 45.5%, respectively. The multivariate analysis showed that the following variables were associated with a shorter survival: metastases at diagnosis (P < .001), necrosis grades 1 and 2 (P = .046), and tumor size (P = .0071). Conclusion The overall 5- and 10-year survival rates were lower than the rates reported in North American and European trials. A pattern of advanced disease at diagnosis was often present, with a high proportion of patients having metastases (20.8%) and large tumor size (42.9%). However, these features were not necessarily associated with longer duration of prediagnostic symptoms. These findings were considered in the strategic planning of the current Brazilian cooperative study, with the aim of improving survival and quality of life of a large number of patients with OS.
Diagnostic Performance of Whole Body Dual Modality 18F-FDG PET/CT Imaging for N- and M-Staging of Malignant Melanoma: Experience With 250 Consecutive Patients
Authors: Reinhardt Michael J. , Joe Alexius Y. , Jaeger Ursula , Huber Andrea , Matthies Alexander , Bucerius Jan , Roedel Roland , Strunk Holger , Bieber Thomas , Biersack Hans-Juergen , Tüting Thomas 
Published: February 2006

Purpose To assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) for N- and M-staging of cutaneous melanoma. Patients and Methods This is a retrospective and blinded study of 250 consecutive patients (105 women, 145 men; age 58 ± 16 years) who underwent FDG-PET/CT for staging of cutaneous melanoma at different time points in the course of disease. Whole-body FDG-PET/CT was performed 101 ± 21 minutes postinjection of 371 ± 41 MBq FDG. Diagnostic accuracy for N- and M-staging was determined for CT alone, PET alone, and PET/CT. Results PET/CT detected significantly more visceral and nonvisceral metastases than PET alone and CT alone (98.7%, 88.8%, and 69.7%, respectively). PET/CT imaging thus provided significantly more accurate interpretations regarding overall N- and M-staging than PET alone and CT alone. Overall N- and M-stage was correctly determined by PET/CT in 243 of 250 patients (97.2%; 95% CI, 95.2% to 99.4%) compared with 232 patients (92.8%; 95% CI, 89.6% to 96.0%) by PET, and 197 patients (78.8%; 95% CI, 73.7% to 83.9%) by CT. All differences were significant. Accuracy of PET/CT was significantly higher than that of PET and CT for M-staging (0.98 v 0.93 and 0.84) and significantly higher than that of CT for N-Staging (0.98 v 0.86). Change of treatment according to PET/CT findings occurred in 121 patients (48.4%). Conclusion The diagnostic performance of FDG-PET/CT for N- and M-staging of melanoma patients suggests its use for whole-body tumor staging, especially for detection or exclusion of distant metastases.
Phase I Trial Evaluating the Safety of Bevacizumab With Concurrent Radiotherapy and Capecitabine in Locally Advanced Pancreatic Cancer
Authors: Crane Christopher H. , Ellis Lee M. , Abbruzzese James L. , Amos Christina , Xiong Henry Q. , Ho Linus , Evans Douglas B. , Tamm Eric P. , Ng Chaan , Pisters Peter W.T. , Charnsangavej Chusilp , Delclos Marc E. , O'Reilly Michael , Lee Jeffrey E. , Wolff Robert A. 
Published: February 2006

Purpose To study the safety of bevacizumab with capecitabine-based chemoradiotherapy. Patients and Methods Patients with inoperable pancreatic adenocarcinoma received bevacizumab 2 weeks before radiotherapy (50.4 Gy treating the primary tumor and gross adenopathy), every 2 weeks during radiotherapy (12 patients each at 2.5, 5.0, 7.5, and 10 mg/kg), and after radiotherapy until disease progression. Capecitabine was administered on days 14 through 52 (650 mg/m2 orally twice daily for the first six patients; 825 mg/m2 for the remaining patients). Results Significant acute gastrointestinal (43% grade 2; 4% grade 3), hand and foot syndrome (21% grade 2), and transient hematologic (8% grade 3 or greater) events were uncommon with protocol mandated dose reductions of capecitabine grade 2 toxicity (43% of patients). Among the first 30 patients treated, three patients had tumor-associated bleeding duodenal ulcers, and one had a contained duodenal perforation. No additional bleeding events occurred among the final 18 patients after patients with duodenal involvement by tumor were excluded. Nine (20%) of 46 assessable patients had confirmed partial responses until distant progression for a median of 6.2 months. Four patients have undergone pancreaticoduodenectomy without perioperative complication. The median survival was 11.6 months (95% CI, 9.6 to 13.6), from the start of protocol therapy. Conclusion Concurrent bevacizumab did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiotherapy regimen. However, ulceration and bleeding in the radiation field possibly related to bevacizumab occurred when tumor involved the duodenal mucosa. The encouraging efficacy end points suggest that the further study of bevacizumab with chemoradiotherapy is warranted.
Characterization of CD4+CD25+ Regulatory T Cells in Patients Treated With High-Dose Interleukin-2 for Metastatic Melanoma or Renal Cell Carcinoma
Authors: Cesana Giovanni C. , DeRaffele Gail , Cohen Seth , Moroziewicz Dorota , Mitcham Josephine , Stoutenburg John , Cheung Ken , Hesdorffer Charles , Kim-Schulze Seunghee , Kaufman Howard L. 
Published: February 2006

Purpose To characterize the number and functional status of CD4+CD25+ regulatory T cells (Tregs) in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC) treated with high-dose bolus interleukin-2 (IL-2). Patients and Methods Patients with MM or RCC treated with high-dose bolus IL-2 (600,000 IU/kg every 8 hours) at a single center provided pre- and post-treatment whole blood specimens. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, separated into cellular subsets, and analyzed by flow cytometry or used for in vitro proliferation assays. Results Between September 2003 and July 2005 57 patients were enrolled in the study with 48 patients available for analysis (45 MM, 12 RCC). Tregs were defined as CD4+CD25hi T cells, and this subset was significantly elevated in the cancer patients compared with normal donors (7.75% v 2.24%). The CD4+CD25hi T-cell pool in the patients constitutively expressed intracellular FoxP3, CTLA-4, and produced high amounts of IL-10. The Tregs were CCR7+ with 50% representing naïve and 50% central-memory T cells. The cells were functionally suppressive in mixed in vitro proliferation assays. Following IL-2 administration, the number and frequency of Tregs increased in patients with progressive disease but returned to normal levels in patients with objective clinical responses. Conclusion The number of Tregs, defined as CD4+CD25hi T cells is increased in patients with MM and RCC. High-dose IL-2 resulted in a significant decrease of Tregs in those patients achieving an objective clinical response to IL-2 therapy.
Multicenter Validation of a Gene Expression–Based Prognostic Signature in Lymph Node–Negative Primary Breast Cancer
Authors: Foekens John A. , Atkins David , Zhang Yi , Sweep Fred C.G.J. , Harbeck Nadia , Paradiso Angelo , Cufer Tanja , Sieuwerts Anieta M. , Talantov Dmitri , Span Paul N. , Tjan-Heijnen Vivianne C.G. , Zito Alfredo F. , Specht Katja , Hoefler Heinz , Golouh Rastko , Schittulli Francesco , Schmitt Manfred , Beex Louk V.A.M. , Klijn Jan G.M. , Wang Yixin 
Published: February 2006

Purpose We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. Patients and Methods Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. Results In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. Conclusion Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.
Social Networks, Social Support, and Survival After Breast Cancer Diagnosis
Authors: Kroenke Candyce H. , Kubzansky Laura D. , Schernhammer Eva S. , Holmes Michelle D. , Kawachi Ichiro 
Published: February 2006

PurposeWe prospectively examined social ties and survival after breast cancer diagnosis.Patients and MethodsParticipants included 2,835 women from the Nurses' Health Study who were diagnosed with stages 1 to 4 breast cancer between 1992 and 2002. Of these women, 224 deaths (107 of these related to breast cancer) accrued to the year 2004. Social networks were assessed in 1992, 1996, and 2000 with the Berkman-Syme Social Networks Index. Social support was assessed in 1992 and 2000 as the presence and availability of a confidant. Cox proportional hazards models were used in prospective analyses of social networks and support, both before and following diagnosis, and subsequent survival.ResultsIn multivariate-adjusted analyses, women who were socially isolated before diagnosis had a subsequent 66% increased risk of all-cause mortality (HR = 1.66; 95% CI, 1.04 to 2.65) and a two-fold increased risk of breast cancer mortality (HR = 2.14; 95% CI, 1.11 to 4.12) compared with women who were socially integrated. Women without close relatives (HR = 2.65; 95% CI, 1.03 to 6.82), friends (HR = 4.06; 95% CI, 1.40 to 11.75), or living children (HR = 5.62; 95% CI, 1.20 to 26.46) had elevated risks of breast cancer mortality and of all-cause mortality compared with those with the most social ties. Neither participation in religious or community activities nor having a confidant was related to outcomes. Effect estimates were similar in analyses of postdiagnosis networks.ConclusionSocially isolated women had an elevated risk of mortality after a diagnosis of breast cancer, likely because of a lack of access to care, specifically beneficial caregiving from friends, relatives, and adult children.
Air breathing of aquatic burrow-dwelling eel goby,Odontamblyopus lacepedii(Gobiidae: Amblyopinae)
Authors: Gonzales Tomas T. , Katoh Masaya , Ishimatsu Atsushi 
Published: March 2006

SUMMARYOdontamblyopus lacepedii is an eel goby that inhabits both coastal waters and intertidal zones in East Asia, including Japan. The fish excavates burrows in mudflats but, unlike the sympatric amphibious mudskippers, it does not emerge but stays in the burrows filled with hypoxic water during low tide. Endoscopic observations of the field burrows demonstrated that the fish breathed air in the burrow opening; air breathing commenced 1.3 h following burrow emersion, when water PO2 was ∼2.8 kPa, with an air-breathing frequency (fAB) of 7.3±2.9 breaths h–1 (mean ± s.d., N=5). Laboratory experiments revealed that the fish is a facultative air breather. It never breathed air in normoxic water (PO2=20.7 kPa) but started bimodal respiration when water PO2 was reduced to 1.0–3.1 kPa. The fish held air inside the mouth and probably used the gills as gas-exchange surfaces since no rich vascularization occurred in the mouth linings. As is known for other air-breathing fishes, fAB increased with decreasing water PO2. Both buccal gas volume (VB) and inspired volume (VI) were significantly correlated with body mass (Mb). At a given Mb, VI was nearly always equal to VB,implying almost complete buccal gas renewal in every breathing cycle. A temporal reduction in expired volume (VE) was probably due to a low aerial gas exchange ratio (CO2 elimination/O2uptake). Air breathing appears to have evolved in O. lacepedii as an adaptation to aquatic hypoxia in the burrows. The acquisition of the novel respiratory capacity enables this species to stay in the burrows during low tide and extends the resident time in the mudflat, thereby increasing its chances of tapping the rich resources of the area.
The ventilatory, cardiac and behavioural responses of resting cuttlefish(Sepia officinalisL.) to sudden visual stimuli
Authors: King Alison J. , Adamo Shelley A. 
Published: March 2006

SUMMARYWhen startled, some animals reduce ventilation rate and heart rate, and become motionless. The function of this response, if any, remains unknown. We used non-invasive ultrasound imaging to monitor the ventilatory, cardiac and postural responses of cuttlefish exposed to sudden visual stimuli. Simultaneously, we recorded cuttlefish behaviour using an overhead video camera. Upon presentation of the sudden visual stimulus (rapidly approaching bird cut-out), cuttlefish rapidly changed the colour and the texture of their skin, taking on characteristics of the Deimatic Display. Cuttlefish also became motionless (behavioural freezing), hyperinflated their mantles, and decreased their ventilation rate and heart rate. We found no evidence of a relationship between the intensity of the Deimatic Display and the intensity of any other measured parameter. Ventilation rate decreased during behavioural freezing. Hyperinflation of the mantle was most intense in preparation for and during behavioural freezing. Heart rate decreases occurred during mantle hyperinflation and were greatest in animals showing the most hyperinflation. Decreased heart rate may not be adaptive per se. Instead, it might be a product of the unusual arrangement of the cuttlefish peripheral vasculature,which could be compressed during mantle hyperinflation. By filling the mantle with water (hyperinflation), this response to sudden stimuli may help cuttlefish prepare for possible flight by jet propulsion, which often follows the Deimatic Display.
Sex differences in food intake and digestive constraints in a nectarivorous bird
Authors: Markman Shai , Tadmor-Melamed Hagar , Arieli Amichai , Izhaki Ido 
Published: March 2006

SUMMARY
Sex-specific foraging behaviour might be influenced by digestive constraints. However, evidence for sex differences in digestive performance is limited. Various physiological traits are known to be body size dependent. Therefore, we hypothesized that body size differences between male and female birds may lead to differences in their digestive characteristics. We predicted that if food intake and digestive functions are only governed by body mass,then males that are heavier than females would have higher food intake, food assimilation efficiency and gut transit time, but not after controlling for the effect of body mass.
We fed a diet of equicaloric solutions of sucrose and a 1:1 mixture of glucose and fructose (hexose mixture) solutions to Palestine sunbirds(Nectarinia osea). When fed sucrose solutions, males had longer transit times but similar absorption efficiencies as females. Transit times,corrected for differences in body mass and food intake, were still longer in males than in females when fed on sucrose solutions. The sex-specific differences in transit time disappeared when the birds were fed the hexose mixture.
Our results suggest that males take longer to digest than females when fed on sucrose-rich nectars as opposed to hexose-rich nectars, and therefore can allow themselves a relatively lower digestive capacity. This may suggest sex-specific co-evolution of sunbirds within mixed plant communities, which have both sucrose- and hexose-rich nectar-producing plants. Furthermore,future studies on digestion in birds may pay attention to sex-specific differences.
A New Efficient Method for Stereoselective Synthesis of 2-Deoxy-C-ribofuranosides
Authors: Mukaiyama Teruaki , Uchiro Hiromi , Hirano Noriyuki , Ishikawa Tatsuya 
Published: March 2006

Abstract
Stereoselective C-glycosylation of 2-deoxyribose derivatives having 3-O-thiocarbamoyl directing group with carbon nucleophiles was successfully carried out by using SiCl(OTf)3 as an activator. Several 2-deoxy-β-C-ribofuranosides which can be easily converted to 2′-deoxy-C-nucleosides were obtained in good yields with high stereoselectivities.
Photochemical Rearrangement of Chlorinated Dibenzo-p-dioxins. Regioselective Carbon–Oxygen Bond Homolysis from the Singlet Excited State, and Carbon–Chlorine Bond Homolysis from the Triplet Excited State
Authors: Kobayashi Takanori , Shimada Jun-ichi , Kitahara Chieko , Haga Naoki 
Published: February 2006

Abstract
UV light irradiation of 1-chloro-, 2-chloro-, 1,2-dichloro-, 2,3-dichloro-, and 2,7-dichlorodibenzo-p-dioxin in methanol leads to regioselective homolysis of carbon–oxygen bond from the singlet excited state to undergo rearrangement into chlorinated 2,2′-biphenols. On the contrary, reaction from the triplet excited state of chlorinated dioxins results in selective formation of dechlorinated congeners without altering the dioxin skeleton.