bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative–(BMS 247550) and Apo-2L/TRAIL–induced apoptosis
Authors: Guo Fei , Nimmanapalli Ramadevi , Paranawithana Shanthi , Wittman Sylvie , Griffin David , Bali Purva , O'Bryan Erica , Fumero Carlos , Wang Hong Gang , Bhalla Kapil 
Published: October 2002

AbstractSecond mitochondria-derived activator of caspases (Smac)/DIABLO is a mitochondrial protein that is released into the cytosol along with cytochrome c (cyt c) during the execution of the intrinsic pathway of apoptosis. Smac/DIABLO promotes apoptosis by neutralizing the inhibitory effect of the inhibitor of apoptosis (IAP) family of proteins on the processing and activities of the effector caspases. Present studies demonstrate that, upon engagement of the mitochondrial pathway of apoptosis, epothilone (Epo) B derivative BMS 247550, a novel nontaxane antimicrotubule agent, as well as the death ligand Apo-2L/TRAIL (tumor necrosis factor-α–related apoptosis-inducing ligand) induce the mitochondrial release and cytosolic accumulation of Smac/DIABLO, along with cyt c, in human acute leukemia Jurkat T cells. While it had no activity alone, ectopic overexpression of Smac/DIABLO or treatment with the N-terminus heptapeptide (Smac-7) or tetrapeptide (Smac-4) of Smac/DIABLO significantly increased Epo B– or Apo-2L/TRAIL–induced processing and PARP cleavage activity of caspase-3. This produced a significant increase in apoptosis of Jurkat cells (P &lt; .05). Increased apoptosis was also associated with the down-regulation of XIAP, cIAP1, and survivin. Along with the increased activity of caspase-3, ectopic overexpression of Smac/DIABLO or cotreatment with Smac-4 also increased Epo B– or Apo-2L/TRAIL–induced processing of caspase-8 and Bid, resulting in enhanced cytosolic accumulation of cyt c. This was not due to increased assembly and activity of Apo-2L/TRAIL–induced DISC (death-inducing signaling complex) but dependent on the feedback activity of caspase-3. These findings demonstrate that cotreatment with the N-terminus Smac/DIABLO peptide is an effective strategy to enhance apoptosis triggered by the death receptor or mitochondrial pathway and may improve the antitumor activity of Apo-2L/TRAIL and Epo B.
First-Line Treatment With Epirubicin and Vinorelbine in Metastatic Breast Cancer
Authors: Vici Patrizia , Colucci Giuseppe , Gebbia Vittorio , Amodio Antonella , Giotta Francesco , Belli Franca , Conti Francesca , Gebbia Nicola , Pezzella Giuseppe , Valerio Maria Rosaria , Brandi Mario , Pisconti Salvatore , Durini Ernesto , Giannarelli Diana , Lopez Massimo 
Published: October 2002

PURPOSE: This phase II multicenter trial was aimed at investigating the activity of epirubicin-vinorelbine combination as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: Ninety-seven patients with metastatic breast cancer and no prior exposure to anthracyclines received the following regimen: epirubicin 100 mg/m2 by intravenous (IV) bolus infusion on day 1 plus vinorelbine 25 mg/m2 by 30-minute IV infusion on days 1 and 5, every 3 weeks for up to eight cycles. All patients also received granulocyte colony-stimulating factor (G- CSF) on days 7 to 12 of every cycle. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 65 out of 92 assessable patients (70.6%; 95% CI, 62% to 80%). Disease remained stable in 17 patients (18.5%). Responses were observed in all disease sites, being 94% in soft tissue, 60% in bone, and 66% in visceral disease. Median time to response, median duration of response, median time to progression, and median overall survival were 2, 9, 10, and 26 months, respectively. The dose-limiting toxicity was neutropenia, which was grade 4 in 36% of the patients, and was accompanied by fever in 26% of the cases. Grade 3 to 4 mucositis was encountered in 28% of the patients. Other toxicities were mild to moderate. No cardiotoxicity was observed. CONCLUSION: The epirubicin-vinorelbine combination with G-CSF support has been shown in this study to be highly active as first-line treatment of metastatic breast cancer patients, with significant although transient toxicity. This justifies further evaluation in the neoadjuvant setting and in early-stage breast cancer.
Superior Survival With Capecitabine Plus Docetaxel Combination Therapy in Anthracycline-Pretreated Patients With Advanced Breast Cancer: Phase III Trial Results
Authors: O’Shaughnessy Joyce , Miles David , Vukelja Svetislava , Moiseyenko Vladimir , Ayoub Jean-Pierre , Cervantes Guadalupe , Fumoleau Pierre , Jones Stephen , Lui Wing-Yiu , Mauriac Louis , Twelves Chris , Van Hazel Guy , Verma Shailendra , Leonard Robert 
Published: October 2002

PURPOSE: Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine, show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in preclinical studies. This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC. PATIENTS AND METHODS: Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m2 twice daily on days 1 to 14 plus docetaxel 75 mg/m2 on day 1 (n = 255) or to docetaxel 100 mg/m2 on day 1 (n = 256). RESULTS: Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression (TTP) (hazard ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P = .0001; median, 6.1 v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P = .0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v 30%, P = .006) compared with docetaxel. Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy, whereas myalgia, arthralgia, and neutropenic fever/sepsis were more common with single-agent docetaxel. More grade 3 adverse events occurred with combination therapy (71% v 49%, respectively), whereas grade 4 events were slightly more common with docetaxel (31% v 25% with combination). CONCLUSION: The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m2, with the manageable toxicity profile, indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m2. Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC.
Overexpression of the Polycythemia Rubra Vera-1 Gene in Essential Thrombocythemia
Authors: Teofili Luciana , Martini Maurizio , Luongo Myriam , Di Mario Antonella , Leone Giuseppe , De Stefano Valerio , Larocca Luigi Maria 
Published: October 2002

PURPOSE: To examine the utility of polycythemia rubra vera-1 (PRV-1)–specific reverse transcriptase polymerase chain reaction (RT-PCR) to discriminate essential thrombocythemia (ET) and polycythemia vera (PV) from secondary thrombocytosis (ST) or secondary erythrocytosis (SE). PATIENTS AND METHODS: We analyzed the expression of PRV-1 in granulocytes isolated from 37 patients with ET, 37 patients with PV, 25 patients with ST, 10 patients with SE, 25 patients with secondary leukocytosis (SL), five patients with chronic myelogenous leukemia (CML), five patients with chronic idiopathic myelofibrosis (IM), five patients with myelodysplastic syndrome (MDS), and 20 normal individuals by PRV-1–specific RT-PCR. In female patients, PRV-1 expression was correlated with clonality analysis as assessed by the human androgen receptor polymorphism assay. RESULTS: PRV-1 was not expressed in granulocytes isolated from normal individuals or from patients with ST, SE, CML, IM, MDS, and inflammatory/infectious SL. On the contrary, all ET patients, 35 of 37 PV patients, and five patients with acute postsurgery and posttraumatic SL overexpressed PRV-1. All the cases with monoclonal hematopoiesis (17 of 21 with ET and 12 of 12 with PV) expressed PRV-1, yet PRV-1 overexpression extended also over the cases of ET showing polyclonal hematopoiesis (four of 20). CONCLUSION: The overexpression of PRV-1 seems to be a useful tool for discriminating ET and PV from ST and SE, thus offering an innovative diagnostic approach on the basis of the detection of positive diagnostic criteria instead of exclusion criteria.
VAMP and Low-Dose, Involved-Field Radiation for Children and Adolescents With Favorable, Early-Stage Hodgkin’s Disease: Results of a Prospective Clinical Trial
Authors: Donaldson Sarah S. , Hudson Melissa M. , Lamborn Kathleen R. , Link Michael P. , Kun Larry , Billett Amy Louise , Marcus Karen C. , Hurwitz Craig A. , Young Jeffrey A. , Tarbell Nancy J. , Weinstein Howard J. 
Published: October 2002

PURPOSE: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin’s disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. PATIENTS AND METHODS: One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin’s disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. RESULTS: With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin’s disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. CONCLUSION: Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin’s disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin’s disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.
Expression of viral and human dUTPase in Epstein‐Barr virus‐associated diseases
Authors: Fleischmann Johann , Kremmer Elisabeth , Greenspan John S. , Grässer Friedrich A. , Niedobitek Gerald 
Published: October 2002

AbstractDeoxyuridine triphosphatase (dUTPase) catalyses the hydrolysis of dUTP to dUMP and pyrophosphate thus preventing the incorporation of uracil into replicating DNA. Previous studies of several virus models have suggested that viral dUTPases may be required for virus replication in resting cells whereas in proliferating cells cellular dUTPase may substitute for a mutant viral protein. Using monoclonal antibodies and immunohistochemistry, Epstein‐Barr virus‐associated non‐neoplastic and neoplastic diseases were studied for the expression of viral and human dUTPases. Oral hairy leukoplakia, an AIDS‐associated lesion of the tongue, is known to support EBV replication in the upper epithelial cell layers. In agreement with this, strong focal expression of EBV dUTPase was detected in the upper epithelial cell layers of oral hairy leukoplakia whereas expression of human dUTPase was confined to the basal proliferative cell compartment. Furthermore, in infectious mononucleosis tonsils, rare scattered small lymphoid cells expressed EBV dUTPase, consistent with the expression pattern of other EBV lytic cycle antigens. These findings are in agreement with the notion that EBV replicates in resting cells. Three EBV‐associated tumours, Hodgkin lymphoma, Burkitt lymphoma and nasopharyngeal carcinoma, lacked detectable expression of EBV dUTPase, in agreement with the notion that EBV infection is largely latent in these tumours. By contrast, expression of human dUTPase was observed regularly in these tumours. These results suggest that EBV dUTPase may be a suitable target for anti‐viral therapy and that inhibitors of human dUTPase should prove useful for the treatment of human tumours, including EBV‐associated cancers. J. Med. Virol. 68:568–573, 2002. © 2002 Wiley‐Liss, Inc.
Long‐term immunogenicity of an inactivated virosome hepatitis A vaccine
Authors: Bovier P.A. , Bock J. , Loutan L. , Farinelli T. , Glueck R. , Herzog C. 
Published: October 2002

AbstractThe aim of this study was to predict the long‐term protection induced after immunisation with inactivated, aluminium‐free virosome hepatitis A vaccine. The study population consisted of adult volunteers enrolled in four different clinical trials. Lower 95% confidence interval limits and seroconversion rate were calculated by using a linear mixed model to estimate the persistence of serum antibodies over time. To assess the robustness of the mathematical model, several sensitivity analyses were performed with more conservative protective threshold (20 mIU/ml vs. 10 mIU/ml), higher yearly decline rate, and exclusion of volunteers who had increasing titres over time. Based on 190 volunteers with at least two valid assessments of titres from year 3 onward, the median duration of protection was 55.5 years, with a lower limit of the 95% CI of 48.7 years. Duration below 25.3 years was predicted for only 5% of the subjects. Women tended to have higher titres to start with, but their rate of decline was higher, resulting in similar duration of protection overall. The use of a more conservative threshold, higher yearly decline rate, and exclusion of volunteers with increasing titres over time did notaffect these results. According to this model, 95% of the volunteers should have anti‐HAV titres above the minimum protective threshold for 20 years or more following immunisation with two doses of this aluminium‐free vaccine. J. Med. Virol. 68:489–493, 2002. © 2002 Wiley‐Liss, Inc.
Teacher beliefs and cultural models: A challenge for science teacher preparation programs
Authors: Bryan Lynn A. , Atwater Mary M. 
Published: October 2002

AbstractThe purpose of this paper is to present an argument for developing science teacher education programs that examine teachers' beliefs about multicultural issues and their impact on science teaching and learning. In the paper, we (a) delineate a rationale for the study of teacher beliefs about issues of culture and its impact on science teaching and learning; (b) assert three major categories of teacher beliefs to examine for designing teacher education programs that aim to meet the challenges of increasingly culturally diverse classrooms; and (c) discuss implications for science teacher education programs and research. Research has shown that knowing teachers' beliefs and designing instruction and experiences to explicitly confront those beliefs facilitate refinement of and/or transformation of beliefs and practices (Bryan & Abell, J Res Sci Teaching, 36, 121–140, 1999; Harrington & Hathaway, J Teacher Education, 46, 275–284, 1995; Hollingsworth, Am Educational Res J, 26(2), 160–189, 1989; Olmedo, J Teaching Teacher Education, 13, 245–258, 1997; Tobin & LaMaster, J Res Sci Teaching, 32, 225–242, 1995). Furthermore, prior to student teaching, preservice teachers need to be at least culturally sensitive teachers (Gillette, In Teacher Thinking in Cultural Contexts, F. A. Rios (Ed.); Albany, NY: State University of New York Press; 1996, pp. 104–128). Science educators need to continue to identify those beliefs and practices that undergird desirable and equitable science instruction. © 2002 Wiley Periodicals, Inc. Sci Ed 86:821–839, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10043
Full fixed cost recovery lot sizing with quantity discounts
Authors: Britney R.R. , Kuzdrall P.J. , Fartuch N. 
Published: October 2002

AbstractPurchasers must often make lot sizing decisions when facing price schedules of price‐quantity discounts. It is important to determine the supplier's pricing philosophy when establishing a solution procedure.One approach is to evaluate total costs at all of the appropriate break points. This offers limited information: a lot size and a set of total costs. This is especially true in the case of full fixed cost recovery pricing. In actual practice price schedules can be extremely lengthy: indeed, it may be in the supplier's best interests to offer comprehensive discount schedules. This situation complicates the purchaser's decision making process.An efficient alternative, which solves the price‐quantity discount problem when the supplier insists on a full fixed cost recovery schedule, is presented. Computations are reduced to a few simple steps; the result is a least total cost lot size for a simple linear package price model given parameters obtained by an appropriate analysis of the supplier's price‐quantity discount schedule. A starting point is determined and the choice of the lot size is made using a simple criterion. Rapid convergence is assured, given a reasonably well‐behaved schedule.
Scheduling operating room surgical procedures with early and late completion penalty costs
Authors: Charnetski J.R. 
Published: October 2002

AbstractThis work explores the impact of a statistical scheduling technique on two classes of idle times in hospital operating suites. Initially, a mathematical model designed to minimize a weighted sum of the two types of idle time was constructed and optimized. However the minimum solution obtained presented large inequities in the distribution of idle time costs. An example demonstrates the disproportionately high waiting time costs found for one type of waiting cost relative to the other idle time cost. Because the two types of costs were to be absorbed by two different groups, this type of optimal solution was deemed to be unacceptable. For this reason, an “equalizing” solution approach was developed.To provide a realistic basis for the model, over 2,000 actual surgical procedure times were used to model the operation of an operating room suite. The operation was then simulated using a two‐stage Monte Carlo method to approximate the distribution of times and procedure types. Idle time functions for early and late completion were then statistically fitted to obtain estimates of the expected idle times as a function of the amount of time scheduled by procedure type. Both types of solution, the optimizing and the equalizing, were examined.By using the ratio of the two types of idle time costs, we were able to avoid the problem of having to attach specific numerical values to the individual waiting time costs. Both solutions provided capacity/utilization ranges for effective scheduling to either minimize or equalize the two types of costs. Suggestions for implementation using computer‐assisted scheduling methods are discussed.
A polynomial goal programming approach to a class of quality control problems
Authors: Kumar Tayi Giri 
Published: October 2002

AbstractThe traditional quality control approach based on statistical tools has been very useful and effective when output and input qualities can be denned in terms of a single characteristic. However, in process industries such as paper, the output quality is denned in terms of two or more distinct characteristics; hence, reducing the deviation of one output characteristic from its permissible limits could result in forcing other output and/or input characteristics to deviate from their respective limits. Compounding this phenomenon is the fact that most of these industries produce substantial amounts of pollutants whose characteristics are a function of the input and output characteristics. Thus, with increasing costs of waste treatment and stringent pollution standards, there arises a notion of a trade‐off between attaining market specified output characteristics and meeting federally regulated pollution standards.In this article a general process quality control problem has been formulated that reflects the above trade‐off both in terms of a linear and a polynomial goal programming problem. Major advantages and differences between the two formulations are highlighted and illustrated with a practical example drawn from the paper industry.Three separate cases each with different priorities assigned to the output, pollutant and input characteristics are developed and solved under both formulations. Based on the analysis it is observed that the different solutions that result are contingent on the assumptions concerning the priorities associated with each goal and the manner by which one chooses to incorporate tradeoffs between goals in the objective function. Additionally, it is found that the solutions obtained under polynomial goal programming formulation are more conducive for implementation in practical quality control contexts.
An evaluation of overtime policies for a repair shop
Authors: Scudder Gary D. 
Published: October 2002

AbstractThis article presents the first attempt to develop and examine overtime policies for a repair shop environment. Overtime is used to augment repair capacity as needed to offset short‐term demand fluctuations. If overtime provides sufficient additional repair capacity, it may be possible to reduce investment in spare parts inventory.The use of overtime in a repair shop requires managerial attention to several issues. In this article, the following five issues are examined: The relationship between overtime policies and spares stocking levels The timing of overtime—reactive or proactive The amount of overtime to use The level in the product structure at which overtime is most beneficial The priority scheduling and labor assignment policies usedSix overtime policies are developed that explore the above issues. These are examined using a simulation model of a hypothetical repair shop. Since the focus of the article is on overtime policies, a single labor assignment policy is used in conjunction with two priority scheduling rules.The results indicate that reactive overtime policies work well in this environment and overtime is most effective at the lowest level of the product structure, where repair times are relatively shorter. In addition, lowest level parts provide more usage flexibility to handle anticipated future failures.
Methods of cell formation in group technology: A framework for evaluation
Authors: Vakharia Asoo J. 
Published: October 2002

AbstractGroup technology is a manufacturing philosophy that attempts to provide some of the operational advantages of a line layout while maintaining some of the strategic advantages of the job shop layout. In designing a productive process that will adopt this manufacturing strategy, one of the primary problems encountered is the formation of component families and production cells. The production cell is a group of machines or processes of functionally dissimilar types that are placed together and dedicated to the manufacture of a specific range of component families.Several researchers in operations management have proposed methods of forming production cells and component families. These methods differ in terms of information requirements and also in terms of the final cell design. Furthermore, the objectives for each method are quite different and it thus seems that the focus has been on the method rather than its appropriateness in a particular situation. This article reviews some of the most publicized methods of group formation and analyzes the type of cells that could be formed using these methods. Subsequently, an evaluative framework is presented where the relative advantages of each type of production cell are discussed in terms of several strategic and operational factors. This framework is of particular use as it highlights the fact that in implementing a cellular manufacturing system, most organizations will face a trade‐off of strategic and operational “costs.” Finally, the appropriateness of the cell types with respect to the degree of customer interaction is also discussed.