bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Chemotherapy in Resectable Oral Cavity Squamous Cell Cancer: A Randomized Controlled Trial
Authors: Licitra Lisa , Grandi Cesare , Guzzo Marco , Mariani Luigi , Vullo Salvatore Lo , Valvo Francesca , Quattrone Pasquale , Valagussa Pinuccia , Bonadonna Gianni , Molinari Roberto , Cantù Giulio 
Published: January 2003

Purpose: Prognosis of patients with advanced oral cavity cancer is worth improving. Chemotherapy has been reported to be especially active in oral cavity tumors. Here we repeat the results of a randomized, multicenter trial enrolling patients with a resectable, stage T2–T4 (> 3 cm), N0–N2, M0 untreated, squamous cell carcinoma of the oral cavity. Patients and Methods: Patients were randomly assigned to three cycles of cisplatin and fluorouracil followed by surgery (chemotherapy arm) or surgery alone (control arm). In both arms, postoperative radiotherapy was reserved to high-risk patients, and surgery was modulated depending on the tumor’s closeness to the mandible. Patients’ accrual was opened in 1989 and closed in 1999. It included 195 patients. Results: In the chemotherapy arm, three toxic deaths were recorded. No significant difference in overall survival was found. Five-year overall survival was, for both arms, 55%. Postoperative radiotherapy was administered in 33% of patients in the chemotherapy arm, versus 46% in the control arm. A mandible resection was performed in 52% of patients in the control arm, versus 31% in the chemotherapy arm. Conclusion: The addition of primary chemotherapy to standard surgery was unable to improve survival. However, in this study, primary chemotherapy seemed to play a role in reducing the number of patients who needed to undergo mandibulectomy and/or radiation therapy. Variations in the criteria used to select patients for these treatment options may make it difficult to generalize these results, but there appears to be room for using preoperative chemotherapy to spare demolitive surgery and/or radiation therapy in patients with advanced, resectable oral cavity cancer.
Morphologic Dysplasia in De Novo Acute Myeloid Leukemia (AML) Is Related to Unfavorable Cytogenetics but Has No Independent Prognostic Relevance Under the Conditions of Intensive Induction Therapy: Results of a Multiparameter Analysis From the German AML Cooperative Group Studies
Authors: Haferlach Torsten , Schoch Claudia , Löffler Helmut , Gassmann Winfried , Kern Wolfgang , Schnittger Susanne , Fonatsch Christa , Ludwig Wolf-Dieter , Wuchter Christian , Schlegelberger Brigitte , Staib Peter , Reichle Albrecht , Kubica Uschi , Eimermacher Hartmut , Balleisen Leopold , Grüneisen Andreas , Haase Detlef , Aul Carlo , Karow Jochen , Lengfelder Eva , Wörmann Bernhard , Heinecke Achim , Sauerland Maria Cristina , Büchner Thomas , Hiddemann Wolfgang 
Published: January 2003

Purpose: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. Patients and Methods: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. Results: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P < .001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P < .001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. Conclusion: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.
Prognostic Scoring System for Primary CNS Lymphomas: The International Extranodal Lymphoma Study Group Experience
Authors: Ferreri Andrés J.M. , Blay Jean-Yves , Reni Michele , Pasini Felice , Spina Michele , Ambrosetti Achille , Calderoni Antonello , Rossi Andrea , Vavassori Vittorio , Conconi Annarita , Devizzi Liliana , Berger Françoise , Ponzoni Maurilio , Borisch Bettina , Tinguely Marianne , Cerati Michele , Milani Mario , Orvieto Enrico , Sanchez Juvenal , Chevreau Christine , Dell’Oro Stefania , Zucca Emanuele , Cavalli Franco 
Published: January 2003

Purpose: To identify survival predictors and to design a prognostic score useful for distinguishing risk groups in immunocompetent patients with primary CNS lymphomas (PCNSL). Patients and Methods: The prognostic role of patient-, lymphoma-, and treatment-related variables was analyzed in a multicenter series of 378 PCNSL patients treated at 23 cancer centers from five different countries. Results: Age more than 60 years, performance status (PS) more than 1, elevated lactate dehydrogenase (LDH) serum level, high CSF protein concentration, and involvement of deep regions of the brain (periventricular regions, basal ganglia, brainstem, and/or cerebellum) were significantly and independently associated with a worse survival. These five variables were used to design a prognostic score. Each variable was assigned a value of either 0, if favorable, or 1, if unfavorable. The values were then added together to arrive at a final score, which was tested in 105 assessable patients for which complete data of all five variables were available. The 2-year overall survival (OS) ± SD was 80% ± 8%, 48% ± 7%, and 15% ± 7% (P = .00001) for patients with zero to one, two to three, and four to five unfavorable features, respectively. The prognostic role of this score was confirmed by limiting analysis to assessable patients treated with high-dose methotrexate-based chemotherapy (2-year OS ± SD: 85% ± 8%, 57% ± 8%, and 24% ± 11%; P = .0004). Conclusion: Age, PS, LDH serum level, CSF protein concentration, and involvement of deep structures of the brain were independent predictors of survival. A prognostic score including these five parameters seems advisable in distinguishing different risk groups in PCNSL patients. The proposed score and its relevance in therapeutic decision deserve to be validated in further studies.
Evaluation of Monoclonal Humanized Anti-HER2 Antibody, Trastuzumab, in Patients With Recurrent or Refractory Ovarian or Primary Peritoneal Carcinoma With Overexpression of HER2: A Phase II Trial of the Gynecologic Oncology Group
Authors: Bookman Michael A. , Darcy Kathleen M. , Clarke-Pearson Daniel , Boothby Richard A. , Horowitz Ira R. 
Published: January 2003

Purpose: To evaluate the feasibility, toxicity, and efficacy of single-agent monoclonal antibody therapy targeting the human epidermal growth factor receptor 2 (HER2)/neu receptor in ovarian and primary peritoneal carcinoma. Patients and Methods: Eligible patients had measurable persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with 2+ or 3+ HER2 overexpression documented by immunohistochemistry. Intravenous trastuzumab was administered initially at a dose of 4 mg/kg, then weekly at 2 mg/kg. Patients without progressive disease or excessive toxicity could continue treatment indefinitely. Those with stable or responding disease at 8 weeks were offered treatment at a higher weekly dose (4 mg/kg) at time of progression. Patient sera were analyzed for the presence of the soluble extracellular domain of HER2, host antibodies against trastuzumab, and trastuzumab pharmacokinetics. Results: A total of 837 tumor samples were screened for HER2 expression, and 95 patients (11.4%) exhibited the requisite 2+/3+ expression level. Forty-five patients, all of whom received prior chemotherapy, were entered, and 41 were deemed eligible and assessable. There were only mild expected toxicities and no treatment-related deaths. Although an elevated level of the soluble extracellular domain of HER2 was detected in eight of 24 patients, serum HER2 was not associated with clinical outcome. There was no evidence of host antitrastuzumab antibody formation. Serum concentrations of trastuzumab gradually increased with continued therapy. An overall response rate of 7.3% included one complete and two partial responses. Median treatment duration was 8 weeks (range, 2 to 104 weeks), and median progression-free interval was 2.0 months. Conclusion: The clinical value of single-agent trastuzumab in recurrent ovarian cancer is limited by the low frequency of HER2 overexpression and low rate of objective response among patients with HER2 overexpression.
Feasibility and Compliance of Automated Measurement of Quality of Life in Oncology Practice
Authors: Wright E.P. , Selby P.J. , Crawford M. , Gillibrand A. , Johnston C. , Perren T.J. , Rush R. , Smith A. , Velikova G. , Watson K. , Gould A. , Cull A. 
Published: January 2003

Purpose: Systematic quality-of-life (QOL) assessment may have value in oncology practice by increasing awareness of a wide range of issues, possibly increasing detection of psychologic morbidity, social problems, and changes in physical status, and improving care and its outcomes. However, logistic problems are substantial. Automated systems solve many of these problems. We field-tested the feasibility and compliance that can be achieved using a computer touchscreen system in two consecutive studies. Patients and Methods: In study 1, a prospective cohort of 272 patients was offered QOL assessment at each clinic appointment for 6 months. In study 2, all patients (N = 1,291) were offered QOL assessment as part of clinic routine during a 12-week period. Results: In study 1, 82% of patients agreed to take part, but over time, compliance was poor (median, 40%; mean, 43%) and deteriorated with longer follow-up. In study 2, the overall compliance was greatly increased (median, 100%; mean, 70%), and compliance was retained over multiple visits. In study 1, compliance was better in younger patients, males, and socially advantaged patients, but was not affected by the presence of depression or anxiety, or QOL. In the second study, building on experience in the first study, data collection and storage in the computer system was excellent, achieving 98% of collected data stored in one center. In general, patients were comfortable with the computers and the approach. Data collection on the wards was more difficult and less complete than in clinics, especially for patients undergoing acute admissions. Conclusion: Feasibility with higher compliance was demonstrated in study 2, in which the data collection was integrated into routine care, and can be improved with further technical initiatives and education of staff.
Phase I Pharmacokinetic and Pharmacodynamic Study of Recombinant Human Endostatin in Patients With Advanced Solid Tumors
Authors: Thomas James P. , Arzoomanian Rhoda Z. , Alberti Dona , Marnocha Rebecca , Lee Fred , Friedl Andreas , Tutsch Kendra , Dresen Amy , Geiger Peter , Pluda James , Fogler William , Schiller Joan H. , Wilding George 
Published: January 2003

Purpose: Endostatin is the first endogenous angiogenesis inhibitor to enter clinical trials. Laboratory investigations with endostatin have indicated broad antitumor activity coupled with remarkably low toxicity. A phase I trial of recombinant human endostatin was designed to evaluate toxicity and explore biologic effectiveness in patients with refractory solid tumors. Patients and Methods: Endostatin was administered as a 1-hour intravenous infusion given daily for a 28-day cycle. A starting dose of 30 mg/m2 was explored with subsequent dose escalations of 60, 100, 150, 225, and 300 mg/m2. Assessment of serum pharmacokinetics was performed on all 21 patients. Western blot assay and mass spectroscopy were employed to evaluate endostatin metabolism. Circulating levels of endogenous proangiogenic growth factors were examined. Tumor and tumor blood supply were imaged by dynamic computed tomography (CT), magnetic resonance imaging, ultrasound, and positron emission tomography. Results: Endostatin given on this schedule was essentially free of significant drug-related toxicity. Two transient episodes of grade 1 rash were observed. No clinical responses were observed. Endostatin pharmacokinetics were linear with dose, and serum concentrations were achieved that are associated with antitumor activity in preclinical models. No aggregate effect on circulating proangiogenic growth factors were seen, although several patients exhibited persistent declines in vascular endothelial growth factor levels while enrolled in the study. A few patients demonstrated changes in their dynamic CT scans suggestive of a decline in microvessel density, although overall, no consistent effect of endostatin on tumor vasculature was seen. Conclusion: Endostatin given daily as a 1-hour intravenous infusion was well tolerated without dose-limiting toxicity at doses up to 300 mg/m2.
The effects of information on producer and consumer incentives to undertake food safety efforts: A theoretical model and policy implications
Authors: Elbasha* Elamin H. , Riggs T. Lynn 
Published: January 2003

AbstractFood safety presents a double moral hazard problem. This author develops a model of food safety where consumers and producers undertake unobservable preventive measures to reduce the probability of a food‐borne illness. Losses from a food‐borne illness are shared by consumers and producers according to the existing tort law. We characterize the optimal solution and show that this risk‐sharing arrangement and imperfect information create an incentive problem where suboptimal levels of precautions by producers and consumers are attained in a noncooperative Nash equilibrium solution. We conduct comparative static analysis to trace out the effects of changes in the size of losses, the degree of orientation of the legal system, and government regulation of information provision on precautions undertaken by consumers and producers. [EconLit citations: L150, Q180.] © 2003 Wiley Periodicals, Inc. Agribusiness 19: 29–42, 2003.
Life history and the competitive environment: trajectories of growth, maturation, and reproductive output among Chacma baboons
Authors: Johnson Sara E. 
Published: January 2003

AbstractThe social environment is a key feature influencing primate life histories. Chacma baboons (Papio hamadryas ursinus) are a female‐bonded species with a strict linear dominance hierarchy. In this species, the allocation of energy to competing demands of growth and reproduction is hypothesized to vary as a function of competitive ability, which in turn increases with social rank. Since growth rate is a major component of life history models, measures of age‐specific growth were used to analyze variation in life history traits across social ranks. Weights of 42 immature baboons were obtained without sedation or baiting from a troop of well‐habituated chacma baboons in the Okavango Delta, Botswana. Using demographic and weight data from this wild population, five main findings emerged: 1) Weight for age and growth rate of infant and juvenile females are positively associated with maternal rank. 2) Male growth is not influenced by maternal rank. 3) Female growth shows smaller variation across feeding conditions than male growth. 4) Low‐ranking adult females continue investment in offspring through prolonged lactation until they reach a weight comparable to that of high‐ranking infants. 5) The benefit of rank to reproductive success shown in this study is 0.83 additional offspring. Reproductive span determined predominantly by age at maturation contributes 27–38% to the difference in expected number of offspring by rank, vs. 62–73% due to reproductive rate. These findings have major implications for understanding the role of social environment in phenotypic plasticity of life history traits, and in the evolution of primate life histories. Am J Phys Anthropol 120:83–98, 2003. © 2003 Wiley‐Liss, Inc.
Postmarital residence and biological variation at Pueblo Bonito
Authors: Schillaci Michael A. , Stojanowski Christopher M. 
Published: January 2003

AbstractAlthough the social organization of many of the present‐day pueblos of the American Southwest is well‐described in the anthropological literature, many aspects of prehistoric Puebloan social organization have received limited attention since initial investigations of postmarital residence in the 1960s and 1970s. This paper examines postmarital residence at the Chaco Canyon great house of Pueblo Bonito, using biological data. Our findings are inconsistent with the previously well‐accepted hypothesis that the Pueblo II and Pueblo III occupants of the San Juan Basin conformed to a socially prescribed pattern of matrilocal residence with matrilineal descent. Univariate variance differences for nine craniometric variables indicate a pattern of increased female variability consistent with patrilocal/bilocal residence. The results of multivariate determinant ratio analyses are in agreement with the univariate results, suggesting the possibility of a patrilocal or bilocal residence preference at Pueblo Bonito. These findings are inconsistent with the notion that the female‐based system of matrilocal residence with matrilineal descent observed among the present‐day Western Pueblos was the ancestral Anasazi condition. Am J Phys Anthropol 120:1–15, 2003. © 2003 Wiley‐Liss, Inc.
Prominent expression of lysyl oxidase during mouse embryonic cardiovascular development
Authors: Tsuda Takeshi , Pan Te‐Cheng , Evangelisti Lucia , Chu Mon‐Li 
Published: January 2003

AbstractBy mRNA differential display in mouse hearts, lysyl oxidase (Lox), a key enzyme catalyzing cross‐links in elastin and collagens, was found to be up‐regulated between embryonic days 11 (E11) and 13 (E13). This was confirmed by semiquantitative RT‐PCR. We analyzed its spatio‐temporal expression pattern by in situ hybridization in regard to the development of myocardial cells, endocardial cushion tissue, aortic arch vessels, and epicardium. Anat Rec Part A 270A:93–96, 2003. © 2003 Wiley‐Liss, Inc.
Embryonic development of coronary vasculature in rats: Corrosion casting studies
Authors: Ratajska Anna , Ciszek Bogdan , Sowińska Agnieszka 
Published: January 2003

AbstractThe aim of this study was to analyze the development of coronary vessels at different stages of embryonic life in rats using corrosion casts and scanning electron microscopy (SEM). We studied morphologic details of vessel maturation, expansion, and pattern formation from the stage of development when the coronary system forms patent connections with the aorta and the right atrium (embryonic day 16 (ED16)) to full‐term fetus (ED21). The internal surface morphologies of the arterial and venous vessel walls were different and were dependent on the distance from the orifice and the capillary system. They also depended on the maturation state of a given vessel. In various branches of the coronary system we demonstrated round, fusiform or polygonal, endothelial cell imprints. The capillary network was dense, however, at the early stages of development, it formed a thin layer over the myocardium. By ED21 capillaries assumed an orientation parallel to the long axes of the cardiac myocytes. During all stages of development, different forms of angiogenesis by intussusceptive growth were observed. Splitting of the vessel wall occurred in two or three points along the vessel, forming two‐ or three‐link chains. Certain areas of vessels resembled doughnuts, from which several sister vessels originated. The coronary arteries were situated deep within the myocardial wall. The major coronary veins were mostly located on the surface of the capillary plexuses of the myocardial wall. In conclusion, this method of vessel casting enables the detection of angiogenesis by intussusceptive growth, and the visualization of a capillary's position to the myocardial wall, thickness of the capillary plexuses, and the internal surface morphology of major vessels. Anat Rec Part A 270A:109–116, 2003. © 2003 Wiley‐Liss, Inc.
Recapitulation of oral mucosal tissues in long‐term organotypic culture
Authors: Chinnathambi Sathivel , Tomanek‐Chalkley Ann , Ludwig Nicholas , King Elizabeth , DeWaard Rose , Johnson Georgia , Wertz Philip W. , Bickenbach Jackie R. 
Published: January 2003

AbstractTo test the influence of fibroblasts on epithelial morphology and expression of keratinocyte proteins and barrier lipids, we bioengineered homotypic and heterotypic oral mucosae and skin using cultured adult human cells. Fibroblasts were allowed to modify collagen type I gels for 2 weeks before keratinocytes were added. The organotypic cultures were then grown at the air–liquid interface for 4 weeks. In homotypic combinations, epithelial morphology and protein expression closely mimicked those in vivo. In heterotypic combinations, the morphology resembled that in vivo and keratinocytes expressed their typical markers, except when skin keratinocytes were recombined with alveolar fibroblasts; they expressed K19, K4, and K13, which is similar to oral mucosal epithelia rather than to the epidermis. Morphologically, the stratum corneum layers were typical for the epithelial tissues. Grafting the bioengineered cultures to the backs of Nude mice did not change the results, suggesting that our findings are not merely a culture phenomenon. Lipid profiles of the homotypic combinations mimicked the profiles found in the normal epithelial tissues, except that the engineered alveolar epithelium expressed more ceramide 2 than that in vivo. In the heterotypic combinations, keratinocytes appeared to control the lipid profile, except in the combination of skin keratinocytes with alveolar fibroblasts, wherein the ceramide profile appeared to be partly that of alveolar epithelium and partly that of epidermis. These results suggest that cultured adult fibroblasts and keratinocytes are sufficient to recapitulate graftable oral tissues, and, except for alveolar fibroblasts, the type of fibroblast had little influence on keratinocyte differentiation. Anat Rec Part A 270A:162–174, 2003. © 2003 Wiley‐Liss, Inc.