bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of TP53 Mutation Is More Relevant Than Microsatellite Instability Status for the Prediction of Disease-Free Survival in Adjuvant-Treated Stage III Colon Cancer Patients
Authors: Westra Jantine L. , Schaapveld Michael , Hollema Harry , de Boer Jelle P. , Kraak Marian M.J. , de Jong Debora , ter Elst Arja , Mulder Nanno H. , Buys Charles H.C.M. , Hofstra Robert M.W. , Plukker John T.M. 
Published: August 2005

Purpose Microsatellite instability (MSI), TP53 mutation, and KRAS mutation status have been reported as prognostic factors in colon cancer. Most studies, however, have included heterogeneous groups of patients with respect to cancer stage. We determined the prognostic relevance of high-frequency MSI (MSI-H), TP53 mutations, and KRAS mutations in a well-defined group of patients with stage III colon cancer (N = 391), randomly assigned for adjuvant treatment with fluorouracil-based chemotherapy. Methods Three hundred ninety-one tumor specimens were available. MSI was determined in 273 specimens, and mutation analyses of TP53 and KRAS were performed in 220 and 205 specimens, respectively. Results In a univariate analysis, MSI-H (44 of 273; 16%) was associated with a longer disease-free survival (DFS; P = .038), but in a multivariate model adjusting for nodal involvement, histology, invasion, and grade of tumor, the association of MSI status with DFS did no longer reach statistical significance, though the risk estimate for microsatellite stability versus MSI-H tumors did not change much. Mutant TP53, found in 116 (53%) of 220 tumors, was associated with a shorter DFS, both in univariate (P = .009) and multivariate analyses (P = .018), whereas KRAS mutations (58 of 205; 28%) did not show any prognostic significance. Conclusion Both mutant TP53 and MSI-H seem to be prognostic indicators for disease-free survival, but only TP53 retains statistical significance after adjusting for clinical heterogeneity. Thus, in adjuvantly treated patients with stage III colon cancer, presence or absence of a TP53 mutation should be considered as a better predictor for DFS than MSI status.
Ecteinascidin-743 (ET-743) for Chemotherapy-Naive Patients With Advanced Soft Tissue Sarcomas: Multicenter Phase II and Pharmacokinetic Study
Authors: Garcia-Carbonero R. , Supko J.G. , Maki R.G. , Manola J. , Ryan D.P. , Harmon D. , Puchalski T.A. , Goss G. , Seiden M.V. , Waxman A. , Quigley M.T. , Lopez T. , Sancho M.A. , Jimeno J. , Guzman C. , Demetri G.D. 
Published: August 2005

Purpose To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). Patients and Methods Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. Results One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = −0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. Conclusion ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.
Sequential Regimen of Chemotherapy, Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation, and Prophylactic Donor Lymphocyte Transfusion in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Schmid Christoph , Schleuning Michael , Ledderose Georg , Tischer Johanna , Kolb Hans-Jochem 
Published: August 2005

Purpose To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m2), cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD). Results Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34+ cell numbers, and in patients with limited GvHD. Conclusion Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.
Multicenter, Randomized Phase II Trial of Oral CI-1033 for Previously Treated Advanced Ovarian Cancer
Authors: Campos Susana , Hamid Oday , Seiden Michael V. , Oza Amit , Plante Marie , Potkul Ronald K. , Lenehan Peter F. , Kaldjian Eric P. , Varterasian Mary L. , Jordan Cheryl , Charbonneau Claudie , Hirte Hal 
Published: August 2005

Purpose To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells. Patients and Methods This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated—a 50-mg and a 200-mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. Results One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest. Conclusion CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability.
Phase II Study of Gefitinib, Fluorouracil, Leucovorin, and Oxaliplatin Therapy in Previously Treated Patients With Metastatic Colorectal Cancer
Authors: Kuo Timothy , Cho Cheryl D. , Halsey Joanne , Wakelee Heather A. , Advani Ranjana H. , Ford James M. , Fisher George A. , Sikic Branimir I. 
Published: August 2005

Purpose To investigate the gefitinib, fluorouracil (FU), leucovorin, and oxaliplatin regimen (IFOX) in previously treated patients with metastatic colorectal cancer. Patients and Methods Eligible patients had stage IV colorectal adenocarcinoma and had demonstrated progression or intolerance to a prior chemotherapy regimen not including oxaliplatin. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin 85 mg/m2 intravenously (IV) during 2 hours on day 1, hours 0 to 2; leucovorin 200 mg/m2 IV on days 1 and 2, hours 0 to 2; FU 400 mg/m2 IV push on days 1 and 2; and FU 600 mg/m2 IV on days 1 and 2, hours 2 to 24 (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg/d administered orally throughout the 14-day cycle. Results Twenty-seven patients were enrolled onto the study. The median number of prior chemotherapy regimens was two, and 74% of all patients received prior irinotecan. Nine of the 27 patients (33%) and six of the 20 patients (30%) who had prior FU and irinotecan had a partial response by Response Evaluation Criteria in Solid Tumors Group criteria. Median overall survival was 12.0 months. Median event-free survival was 5.4 months. Grade 3 to 4 toxicities included neutropenia (48%), diarrhea (48%), nausea (22%), and vomiting (15%). Conclusion IFOX is an active regimen in patients with previously treated metastatic colorectal adenocarcinoma, demonstrating higher response rates than those reported with FOLFOX-4 alone in a similar patient population.
Modeling the Cost of Management Options for Stage I Nonseminomatous Germ Cell Tumors: A Decision Tree Analysis
Authors: Link Richard E. , Allaf Mohamad E. , Pili Roberto , Kavoussi Louis R. 
Published: August 2005

Purpose Patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) have been managed with surveillance, chemotherapy, or retroperitoneal lymphadenectomy (RPLND) with similar survival outcomes. Cost factors influencing the choice of therapy were evaluated using computer-based decision analysis. Methods A detailed model was developed that integrates projected costs for more than 60 possible treatment outcomes. It incorporates primary, adjuvant, and salvage chemotherapy, primary and postchemotherapy RPLND, and both laparoscopic and open surgical approaches. Starting values and probabilities were derived from a comprehensive meta-analysis of the last 25 years of testes cancer literature. Hypothesis testing was performed using sensitivity analysis. Results The model predicts a cost premium for both primary chemotherapy (18.7%) and RPLND (51.7%) compared with surveillance. If laparoscopic RPLND was practiced, the cost premium for primary surgery (29.1%) approached that of chemotherapy (26.4%). Open RPLND was 1.25× as costly as laparoscopic RPLND, primarily because of longer hospitalization. The choice of open RPLND yielded a 6.9% cost premium for a surveillance program in this model. For such a program, primary chemotherapy became cost advantageous when the probability of recurrence during surveillance was more than 46%. Conclusion This model allows a variety of treatment cost hypotheses to be tested. Primary RPLND is never cost advantageous over surveillance or primary chemotherapy. Surgical costs can significantly increase the overall cost of a surveillance program. In stage I patients with high-risk tumor characteristics, primary chemotherapy may have a cost advantage over surveillance.
Initial and Late Resistance to Imatinib in Advanced Gastrointestinal Stromal Tumors Are Predicted by Different Prognostic Factors: A European Organisation for Research and Treatment of Cancer–Italian Sarcoma Group–Australasian Gastrointestinal Trials Group Study
Authors: Van Glabbeke Martine , Verweij Jaap , Casali Paolo G. , Le Cesne Axel , Hohenberger Peter , Ray-Coquard Isabelle , Schlemmer Marcus , van Oosterom Allan T. , Goldstein David , Sciot Raf , Hogendoorn Pancras C.W. , Brown Michelle , Bertulli Rossella , Judson Ian R. 
Published: August 2005

Purpose The aim of this study was to identify factors predicting initial and late resistance of GI stromal tumor (GIST) patients to imatinib and to document the dose-response relationship in the prognostic subgroups. This study is based on the European Organisation for Research and Treatment of Cancer–Italian Sarcoma Group–Australasian Gastrointestinal Trials Group randomized trial comparing two doses of imatinib in advanced disease. Patients and Methods Initial resistance was defined as progression within 3 months of randomization, and late resistance was defined as progression beyond 3 months. Investigated cofactors include imatinib dose, age, sex, performance status, original disease site, site and size of lesions at trial entry, and baseline hematologic and biologic parameters. Results Initial resistance was recorded for 116 (12%) of 934 assessable patients and was independently predicted by the presence of lung and absence of liver metastases, low hemoglobin level, and high granulocyte count. Among 818 patients who were alive and progression free at 3 months, 347 subsequent progressions were recorded, and late resistance was independently predicted by high baseline granulocyte count, primary tumor outside of the stomach, large tumor size, and low initial imatinib dose. The impact of initial dose on late resistance was mainly significant in patients with a high baseline granulocyte count (> 5.109/L) and in patients with tumors of GI origin outside of the stomach and small intestine. Conclusion Our study identifies patients for whom initial and/or long-term treatment needs to be improved and patients who require a high initial dose. Correlation of these results with immunohistochemistry and molecular parameters may further help to understand the biologic mechanisms of resistance.
Adenomatous Polyposis Families That Screen APC Mutation–Negative by Conventional Methods Are Genetically Heterogeneous
Authors: Renkonen Elise T. , Nieminen Pekka , Abdel-Rahman Wael M. , Moisio Anu-Liisa , Järvelä Irma , Arte Sirpa , Järvinen Heikki J. , Peltomäki Päivi 
Published: August 2005

Purpose One third of families with classical adenomatous polyposis (FAP), and a majority of those with attenuated FAP (AFAP), remain APC mutation–negative by conventional methods. Our purpose was to clarify the genetic basis of polyposis and genotype-phenotype correlations in such families. Patients and Methods We studied a cohort of 29 adenomatous polyposis families that had screened APC mutation–negative by the protein truncation test, heteroduplex analysis, and exon-specific sequencing. The APC gene was investigated for large genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA), and for allelic mRNA expression by single nucleotide primer extension (SNuPE). The AXIN2 gene was screened for mutations by sequencing. Results Four families (14%) showed a constitutional deletion of the entire APC gene (three families) or a single exon (one family). Seven families (24%) revealed reduced or extinct mRNA expression from one APC allele in blood, accompanied by loss of heterozygosity in the APC region in six (75%) of eight tumors. In 15 families (52%), possible APC involvement could be neither confirmed nor excluded. Finally, as detailed elsewhere, three families (10%) had germline mutations in genes other than APC, AXIN2 in one family, and MYH in two families. Conclusion “APC mutation–negative” FAP is genetically heterogeneous, and a combination of MLPA and SNuPE is able to link a considerable proportion (38%) to APC. Significant differences were observed in clinical manifestations between subgroups, emphasizing the importance of accurate genetic and clinical characterization for the proper management of such families.
Carbonic anhydrase in the adult mosquito midgut
Authors: del Pilar Corena Maria , VanEkeris Leslie , Salazar Ma. Isabel , Bowers Doria , Fiedler Molly M. , Silverman David , Tu Chingkuang , Linser Paul J. 
Published: August 2005

SUMMARY
We have previously demonstrated the involvement of carbonic anhydrase (CA)in larval mosquito midgut physiology. In this study, we used Hansson's histochemistry to examine the distribution of the enzyme in the midgut of Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, Culex nigripalpus, Ochlerotatus taeniorhynchus, Anopheles albimanus and Anopheles quadrimaculatus adult mosquitoes. Additionally, we quantitated CA content in the anterior and posterior midgut of adult males and females from these species using the 18O isotope exchange method coupled to mass spectrometry. We also tested the effect of CA inhibitors such as methazolamide and acetazolamide in the alkalization of the midgut in females from these species. Our results indicate that CA is present in the midgut of adults from the species studied and that it appears to be preferentially associated with the posterior midgut in both males and females. CA inhibitors appear to have a profound effect on midgut pH indicating that this enzyme might play a key role in the maintenance of this pH.
Performance of guinea fowlNumida meleagrisduring jumping requires storage and release of elastic energy
Authors: Henry Havalee T. , Ellerby David J. , Marsh Richard L. 
Published: August 2005

SUMMARYThe ability of birds to perform effective jumps may play an important role in predator avoidance and flight initiation. Jumping can provide the vertical acceleration necessary for a rapid takeoff, which may be particularly important for ground-dwelling birds such as phasianids. We hypothesized that by making use of elastic energy storage and release, the leg muscles could provide the large power outputs needed for achieving high velocities after takeoff. We investigated the performance of the leg muscles of the guinea fowl Numida meleagris during jumping using kinematic and force-plate analyses. Comparison of the methods indicated that in this species the wings did not supply energy to power takeoff and thus all the work and power came from the leg muscles. Guinea fowl produced a peak vertical force of 5.3 times body weight. Despite having lower muscle-mass-specific power output in comparison to more specialized jumpers, guinea fowl demonstrated surprisingly good performance by producing muscle-mass-specific work outputs of 45 J kg–1, a value approximately two thirds of the maximal expected value for skeletal muscle. The muscle-mass-specific peak power output during jumping was nearly 800 W kg–1, which is more than twice the peak isotonic power estimated for guinea fowl leg muscles. To account for high power outputs, we concluded that energy has to be stored early in the jumps and released later during peak power production, presumably using mechanisms similar to those found in more specialized jumpers.
Cranial kinesis in palaeognathous birds
Authors: Gussekloo Sander W. S. , Bout Ron G. 
Published: August 2005

SUMMARYCranial kinesis in birds is induced by muscles located caudal on the cranium. These forces are transferred onto the moveable parts of the skull via the Pterygoid–Palatinum Complex (PPC). This bony structure therefore plays an essential role in cranial kinesis. In palaeognathous birds the morphology of the PPC is remarkably different from that of neognathous birds and is thought to be related to the specific type of cranial kinesis in palaeognaths known as central rhynchokinesis. We determined whether clear bending zones as found in neognaths are present in the upper bill of paleognaths, and measured bending forces opposing elevation of the upper bill. A static force model was used to calculate the opening forces that can be produced by some of the palaeognathous species. We found that no clear bending zones are present in the upper bill, and bending is expected to occur over the whole length of the upper bill. Muscle forces are more than sufficient to overcome bending forces and to elevate the upper bill. The resistance against bending by the bony elements alone is very low, which might indicate that bending of bony elements can occur during food handling when muscles are not used to stabilise the upper bill. Model calculations suggest that the large processi basipterygoidei play a role in stabilizing the skull elements, when birds have to resist external opening forces on the upper bill as might occur during tearing leafs from plants. We conclude that the specific morphology of the palaeognathous upper bill and PPC are not designed for active cranial kinesis, but are adapted to resist external forces that might cause unwanted elevation of the upper bill during feeding.
The kinematics of feeding and drinking in palaeognathous birds in relation to cranial morphology
Authors: Gussekloo Sander W. S. , Bout Ron G. 
Published: August 2005

SUMMARYCranial kinesis is an important feature in avian feeding behaviour and involves the transmission of quadrate movement to the upper bill by the Pterygoid–Palatinum Complex (PPC). The PPC in Palaeognathae is remarkably different from that found in Neognathae. In this study we analyse whether the special morphology of the PPC is an adaptation to the feeding behaviour of the Palaeognathae. Behavioural analyses of the rhea Rhea americana showed that the feeding behaviour of the rhea is typical `Catch and Throw' behaviour, independent of the size of the food item. Drinking is achieved by a scooping movement followed by a low-amplitude tip-up phase. During feeding rhynchokinetic movements of the upper bill were observed. However, cranial kinesis was limited and may differ from rhynchokinesis in neognathes as a clear bending zone seemed absent. Since the movement patterns are considered very similar to the basic feeding behaviour in neognathous birds it is concluded that the specific morphology of the PPC is not the result of specific functional demands from palaeognathous feeding behaviour.
Mechanisms underlying the production of carapace vibrations and associated waterborne sounds in the American lobster,Homarus americanus
Authors: Henninger Heidi Pye , Watson Winsor H. 
Published: August 2005

SUMMARYAmerican lobsters produce carapace vibrations, which also lead to waterborne acoustic signals, by simultaneously contracting the antagonistic remotor and promotor muscles located at the base of the second antenna. These vibrations have a mean frequency of 183.1 Hz (range 87–261 Hz), range in duration from 68 to 1720 ms (mean 277.1 ms) and lead to waterborne sounds of similar frequencies. Lobsters most often produce these signals using only one pair of muscles at a time and alternate between the muscles of the left and right antennae when making a series of vibrations. Occasionally, they vibrate their carapace by simultaneously contracting both sets of muscles. While the remotor muscle is required for producing carapace vibrations, the promotor appears to play a secondary role. Electrical stimulation of the remotor, but not the promotor, results in the production of vibrations, while lesions of the remotor, but not promotor, eliminate the ability of lobsters to vibrate their carapace. Lobsters of all sizes and both sexes produce these signals when startled, grasped or threatened. However, at this time, the behavioral significance of vibration and/or sound production by American lobsters is not known.