bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in calves
Authors: Landoni Maria Fabiana , Lees Peter 
Published: January 2005

AbstractThe pharmacokinetics (PK) and pharmacodynamics (PD) of (S)‐ and (R)‐ ketoprofen (KTP) enantiomers were studied in calves after intravenous administration of each enantiomer at a dose of 1.5 mg/kg. Pharmacodynamic properties were evaluated using a model of acute inflammation, comprising subcutaneously implanted tissue cages stimulated by intracaveal injection of carrageenan.Chiral inversion of (R)‐KTP to the (S)‐antipode occurred. The R:S ratio in plasma was 33:15 min after administration, decreasing to 1:1 at 8 h. The calculated extent of inversion was 31 ± 7%. The R:S ratio in inflammatory exudate was of the order 3:1 at all the sampling times and the ratio in transudate was approximately 2:1 for 6 h, declining to 1:1 at 30 h. Only (S)‐KTP was detected in biological fluids after administration of this enantiomer. Elimination half‐life was longer for the (S) (2.19 h) than the (R)‐enantiomer (1.30 h) and volume of distribution was also somewhat higher for the (S)‐enantiomer. Body clearance values were 0.119 1/kg/h for (S)‐KTP and 0.151 1/kg/h for the (R)‐antipode. For (R)‐KTP effects obtained were considered as a hybrid, since they potentially reflect the actions of both enantiomers. Concentrations of LTB4and the cytokines interleukin‐1, interleukin‐6, and tumor necrosis factor alpha, in exudate were not significantly affected by either (R)‐ or (S)‐KTP treatments. Inhibition of ex vivo thromboxane B2(TxB2) synthesis, exudate prostaglandin E2(PGE2) synthesis, β‐glucuronidase release (β‐glu), and bradykinin‐induced skin swelling was significant in both treated groups. PK/PD modelling was applied to the (S)‐KTP treatment only. EC50values for inhibition of serum TxB2, exudate PGE2and β‐glu and BK‐induced swelling were 0.047, 0.042, 0.101, and 0.038 μg/ml, respectively. It is concluded that the low EC50values for inhibition of TxB2and PGE2by (S)‐KTP are likely to explain the effects produced by (R)‐KTP administration, since concentrations of (S)‐KTP in exudate of these calves following chiral inversion were at least 5 times higher than the EC50at all sampling times. The data for β‐glu and bradykinin‐induced swelling inhibition indicate possible inhibitory actions of (R)‐KTP as well as (S)‐KTP. © 1995 Wiley‐Liss, Inc.
Validation of a nomogram for predicting disease‐specific survival after an R0 resection for gastric carcinoma
Authors: Peeters Koen C. M. J. , Kattan Michael W. , Hartgrink Henk H. , Kranenbarg Elma Klein , Karpeh Martin S. , Brennan Murray F. , van de Velde Cornelis J. H. 
Published: January 2005

AbstractBACKGROUNDA statistical model for predicting disease‐specific survival in patients with gastric carcinoma, based on a single U.S. institution experience, was tested for validity in a sample of patients treated at different institutions.METHODSThe authors analysed 459 patients from the Dutch Gastric Cancer trial that compared limited (D1) with extended (D2) lymph node dissection. The discrimination ability of the nomogram with respect to 5 and 9‐year disease‐specific survival probabilities was superior to that of the American Joint Committee on Cancer (AJCC) staging system.RESULTSThere was considerable heterogeneity of risk within many of the AJCC stages. Calibration plots suggested that predicted probabilities from the nomogram corresponded closely to actual disease‐specific survival. The gastric carcinoma nomogram performed well when applied to patients treated in a large number of institutions.CONCLUSIONSThe nomogram provided predictions that discriminated better than the AJCC staging system, regardless of the extent of lymph node dissection. Patient counseling and adjuvant therapy decision‐making should benefit from use of the nomogram. Cancer 2005. © 2005 American Cancer Society.
Breast conservation after neoadjuvant chemotherapy
Authors: Chen Allen M. , Meric‐Bernstam Funda , Hunt Kelly K. , Thames Howard D. , Outlaw Elesyia D. , Strom Eric A. , McNeese Marsha D. , Kuerer Henry M. , Ross Merrick I. , Singletary S. Eva , Ames Fredrick C. , Feig Barry W. , Sahin Aysegul A. , Perkins George H. , Babiera Gildy , Hortobagyi Gabriel N. , Buchholz Thomas A. 
Published: January 2005

AbstractBACKGROUNDThe appropriate selection criteria for breast‐conserving therapy (BCT) after neoadjuvant chemotherapy are poorly defined. The purpose of the current report was to develop a prognostic index to help refine selection criteria and to serve as a general framework for clinical decision‐making for patients treated by this multimodality approach.METHODSFrom a group of 340 patients treated with BCT after neoadjuvant chemotherapy, the authors previously determined 4 statistically significant predictors of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR): clinical N2 or N3 disease, residual pathologic tumor size > than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The M. D. Anderson Prognostic Index (MDAPI) was developed by assigning scores of 0 (favorable) or 1 (unfavorable) for each of these 4 variables and using the total to give an overall MDAPI score of 0–4.RESULTSThe MDAPI stratified the 340 patients into 3 subsets with statistically different levels of risk for IBTR and LRR after neoadjuvant chemotherapy and BCT. Actuarial 5‐year IBTR‐free survival rates were 97%, 88%, and 82% for patients in the low (MDAPI overall score 0 or 1, n = 276), intermediate (MDAPI score 2, n = 43), and high (MDAPI score 3 or 4, n = 12) risk groups, respectively (P < 0.001). Corresponding actuarial 5‐year LRR‐free survival rates were 94%, 83%, and 58%, respectively (P < 0.001).CONCLUSIONSPatients with an MDAPI score of 0 or 1, which made up 81% of the study population, had very low rates of IBTR and LRR. The MDAPI enabled the identification of a small group (4%) of patients who are at high risk for IBTR and LRR and who may benefit from alternative locoregional treatment strategies. Cancer 2005. © 2005 American Cancer Society.
Should patients with advanced, incurable cancers ever be sent home with total parenteral nutrition?
Authors: Hoda Daanish , Jatoi Aminah , Burnes Jan , Loprinzi Charles , Kelly Darlene 
Published: January 2005

AbstractBACKGROUNDHome total parenteral nutrition (TPN) can be lifesaving and life sustaining for some patients. However, in patients with advanced, incurable cancer, its role is controversial. A retrospective study was conducted to explore whether home TPN was associated with long‐term survival (≥ 1 year) in patients with metastatic disease and to identify predictive factors to enable its judicious use.METHODSThe records of all adult patients with incurable cancer were identified between 1979 and 1999. Records were reviewed in depth for survival from TPN initiation to death and for a variety of demographic and clinical factors.RESULTSFifty‐two patients were identified. Their median age was 56 years (range, 18–83 years), and 30 (58%) were women. Malignant diagnoses included carcinoid/islet cell tumor (n = 10), ovarian carcinoma (n = 6), amyloidosis/multiple myeloma (n = 6), colorectal carcinoma (n = 5), sarcoma (n = 5), pancreatic carcinoma (n = 4), gastric carcinoma (n = 3), lymphoma (n = 2), pseudomyxoma peritonei (n = 2), and other (n = 9). TPN was initiated for the following reasons (indications are not mutually exclusive): alimentary tract obstruction (n = 20), short bowel syndrome/malabsorption (n = 16), fistula (n = 11), dysmotility (n = 3), nausea/emesis (n = 2), anorexia (n = 2), and mucositis (n = 1). The median time from initiation of TPN to death was 5 months (range, 1–154 months). Sixteen patients survived ≥ 1 year. TPN‐related complications included 18 catheter infections (1 per 2.8 catheter‐years), 4 thromboses, 3 pneumothoraces, and 2 episodes of TPN‐related liver disease. Tumor grade, the interval between diagnosis of metastatic disease and initiation of TPN, the presence of prominent cancer symptoms, and the administration of cancer therapy after TPN were not associated in any way with overall survival.CONCLUSIONSThe initiation of home TPN can be associated with long‐term survival in very select patients with incurable cancer, and complication rates with its use appear acceptable. However, the judicious use of home TPN in this setting requires careful clinical assessment on a patient‐by‐patient basis. Cancer 2005. © 2005 American Cancer Society.
Successful treatment of low‐grade oligodendroglial tumors with a chemotherapy regimen of procarbazine, lomustine, and vincristine
Authors: Stege Elize M. Biemond‐ter , Kros Johan M. , de Bruin Hein G. , Enting R. H. , van Heuvel Irene , Looijenga Leendert H. J. , van der Rijt Carin D. D. , Smitt Peter A. E. Sillevis , van den Bent Martin J. 
Published: January 2005

AbstractBACKGROUNDAnaplastic oligodendroglioma (OD) tumors, especially those with the combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), are sensitive to chemotherapy. Only limited data are available on the role of chemotherapy in low‐grade OD. The authors retrospectively studied the outcome of the procarbazine, lomustine, and vincristine (PCV) chemotherapy regimen in a group of 16 patients with newly diagnosed OD and 5 patients with recurrent low‐grade OD.METHODSTwo groups of patients were studied: newly diagnosed patients with large OD and mixed oligoastrocytomas (OA) and patients with recurrent OD and OA after radiotherapy who still showed nonenhancing tumors. Treatment consisted of standard PCV chemotherapy. In the newly diagnosed and responding patients, radiotherapy was withheld until the time of disease recurrence. Responses were assessed by T2‐weighted magnetic resonance image (MRI) scans. Loss of chromosome 1p and 19q was assessed using fluorescent in situ hybridization with locus‐specific probes.RESULTSThree of five patients with recurrent tumors responded. Thirteen of the 16 newly diagnosed patients showed evidence of response. The median time to disease progression in this group was > 24 months. Only one of these patients experienced disease progression while receiving chemotherapy. Several patients showed a signficant clinical improvement despite only a modest improvement of the tumor on the MRI scans. Even patients without loss of 1p or 19q showed satisfactory responses. No TP53 mutations were found.CONCLUSIONSNewly diagnosed patients with OD tumors, with or without loss of 1p/19q, responded to PCV chemotherapy. Up‐front chemotherapy may be indicated especially for patients with large tumors. MRI scans were of limited value for the assessment of response. A Phase III trial should be initiated to compare radiotherapy with chemotherapy. Cancer 2005. © 2005 American Cancer Society.
Does the number of lymph nodes examined in patients with lymph node‐negative breast carcinoma have prognostic significance?
Authors: Salama Joseph K. , Heimann Ruth , Lin Fen , Mehta Neil , Chmura Steven J. , Singh Rachana , Kao Johnny 
Published: January 2005

AbstractBACKGROUNDThere are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node‐negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor‐free axillary lymph nodes on disease‐free survival (DFS) in two distinct patient populations.METHODSEight hundred thirty‐three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast‐conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1–3 lymph nodes examined, Group 2 had 4–9 lymph nodes examined, Group 3 had 10–20 lymph nodes examined, and Group 4 had > 20 lymph nodes examined.RESULTSIn the mastectomy cohort, with a median follow‐up of 153 months, the 10‐year DFS rate was 70%, 65%, 79%, and 81% for Groups 1–4, respectively. On multivariate analysis, pathologic tumor size (P < 0.001) and the number of lymph nodes examined (P = 0.010) were significant predictors for long‐term DFS. In the breast‐conservation cohort, with a median follow‐up of 53 months, the 5‐year DFS rate was 90%, 91%, 92%, and 95% for Groups 1–4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P = 0.003) and tumor size (P = 0.035).CONCLUSIONSThe recovery of < 10 lymph nodes in lymph node‐negative patients who underwent mastectomy resulted in a 10–15% decreased long‐term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast‐conservation therapy, which included radiation. Cancer 2005. © 2005 American Cancer Society.
Cytokine polymorphisms and hepatocellular carcinoma
Authors: Chung Raymond T. 
Published: January 2005

Regardless of whether monitoring practices change as a result of genotyping, the mandate that replicative hepatitis B virus disease must be treated because of the long‐term risk for necroinflammatory disease, fibrosis, cirrhosis, and hepatocellular carcinoma remains firmly in place.See also pages 740–8.
Cost‐effectiveness of proton radiation in the treatment of childhood medulloblastoma
Authors: Lundkvist Jonas , Ekman Mattias , Ericsson Suzanne Rehn , Jönsson Bengt , Glimelius Bengt 
Published: January 2005

AbstractBACKGROUNDRadiation therapy is an important component in the treatment of medulloblastoma; however, in many patients, it is associated with risk of late adverse events. Proton radiation therapy has potential to reduce the risk of adverse events compared with conventional radiation, but it is associated with a higher treatment cost. The objective of the current study was to assess the cost‐effectiveness of proton therapy compared with conventional radiation therapy in the treatment of childhood medulloblastoma.METHODSThe consequences of radiation therapy were evaluated using a Markov simulation model. Children age 5 years with medulloblastoma were followed. The patients were at risk of several types of adverse events, including hearing loss, intelligence quotient (IQ) loss, hypothyroidism, growth hormone deficiency (GHD), osteoporosis, cardiac disease, and secondary malignancies. The patients also were at risk of death and were divided into risk groups for normal death, death due to tumor recurrence, treatment‐related cardiac death, treatment‐related subsequent tumor death, or treatment‐related other death. A review of the literature was conducted to estimate the parameters in the model.RESULTSThe base‐case results showed that proton therapy was associated with €23,600 in cost savings and 0.68 additional quality‐adjusted life‐years per patient. The analyses showed that reductions in IQ loss and GHD contributed to the greatest part of the cost savings and were the most important parameters for cost‐effectiveness.CONCLUSIONSThe results of the current study indicated that proton radiation therapy can be cost‐effective and cost‐saving compared with conventional radiation therapy in the treatment of children with medulloblastoma if the appropriate patients are selected for the therapy. However, there have been few long‐term follow‐up studies, and more much information on the long‐term consequences of radiation therapy is needed. Cancer 2005. © 2005 American Cancer Society.
Expression of receptor tyrosine kinases epidermal growth factor receptor and HER‐2/neu in synovial sarcoma
Authors: Thomas Dafydd G. , Giordano Thomas J. , Sanders Donita , Biermann Sybil , Sondak Vernon K. , Trent Jonathan C. , Yu Dihua , Pollock Raphael E. , Baker Laurence 
Published: January 2005

AbstractBACKGROUNDSynovial sarcomas are high‐grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER‐2/neu.METHODSArchival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER‐2/neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real‐time polymerase chain reaction (Q‐PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in‐situ hybridization.RESULTSEGFR and HER‐2/neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER‐2/neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER‐2/neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER‐2/neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q‐PCR demonstrated the presence of mRNA for EGFR and HER‐2/neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER‐2/neu were expressed at low concentrations compared with the expression of glyceraldehyde 3‐phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed.CONCLUSIONSEGFR and HER‐2/neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients. Cancer 2005. © 2005 American Cancer Society.
Absence of V599E BRAF mutations in desmoplastic melanomas
Authors: Davison Jon M. , Rosenbaum Eli , Barrett Terry L. , Goldenberg David , Hoque Mohammad O. , Sidransky David , Westra William H. 
Published: January 2005

AbstractBACKGROUNDDesmoplastic melanoma is an uncommon variant of cutaneous melanoma that mimics soft tissue sarcoma both clinically and morphologically. An activating point mutation of the BRAF oncogene has been identified in a high proportion of conventional cutaneous melanomas, but its frequency in the desmoplastic subtype is not known.METHODSThe authors tested 12 desmoplastic melanoma specimens for the thymine (T)→adenine (A) missense mutation at nucleotide 1796 of the BRAF gene using a newly developed assay that employs a novel primer extension method. They also tested 57 vertical growth phase cutaneous nondesmoplastic melanoma specimens.RESULTSThe 1796 T→A mutation was detected in 23 of the 57 conventional cutaneous melanoma specimens but in none of the 12 desmoplastic melanoma specimens (40% vs. 0%; P = 0.0006, Fisher exact 2‐tailed test).CONCLUSIONSThe relative importance of BRAF mutational activation in melanocytic tumorigenesis clearly was not the same across the various subtypes of melanoma, even for melanomas of cutaneous origin that are associated with sun exposure. In contrast to conventional cutaneous melanomas, the desmoplastic variant frequently did not harbor an activating mutation of BRAF. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new therapeutic strategies are developed that target specific genetic alterations. Cancer 2005. © 2005 American Cancer Society.
The safety of interferon‐γ‐1b therapy for invasive fungal infections after hematopoietic stem cell transplantation
Authors: Safdar Amar , Rodriguez Gilhen , Ohmagari Norio , Kontoyiannis Dimitrios P. , Rolston Kenneth V. , Raad Issam I. , Champlin Richard E. 
Published: January 2005

AbstractBACKGROUNDThe restoration of normal immune responses, especially of the T‐helper type 1 immune response, is an important predictor of fungal infection outcome in patients with malignant disease who undergo hematopoietic stem cell transplantation (HSCT). The authors sought to evaluate the safety of adjuvant recombinant interferon‐γ‐1b as an immune‐modulatory therapy HSCT recipients.METHODSThirty‐two patients received interferon‐γ‐1b after undergoing HSCT at the author's institution between 1998 and 2003. A retrospective analysis was undertaken after obtaining permission from the Institutional Review Board.RESULTSTwenty‐six of 32 patients (81%) received allogeneic stem cell grafts. All but 1 patient received interferon‐γ‐1b and antifungals to treat infections; the other patients received interferon‐γ‐1b to promote autologous graft‐versus‐tumor effect. Interferon‐γ‐1b usually was administered at a dose of 50 μg subcutaneously every other day. The median duration (± standard deviation) of interferon‐γ‐1b therapy was 6 ± 6.5 doses (range, 1–29 doses), and the median cumulative dose was 487 ± 453 μg (range, 35–2175 μg). During therapy with interferon‐γ‐1b, fever was common (n = 9 patients; 28%). In 1 patient (3%), new‐onset lymphocytopenia occurred but resolved after cytokine therapy was discontinued; there were no interferon— γ‐1b‐related episodes of neutropenia, thrombocytopenia, anemia, or liver dysfunction. Interferon‐γ‐1b therapy did not precipitate or exacerbate acute or chronic graft‐versus‐host disease (GVHD). In fact, in 2 of 7 patients (29%) with acute GVHD and in 3 of 10 patients (30%) with chronic GVHD, significant improvements in GVHD were noted during therapy with interferon‐γ‐1b. Among the 26 patients with aspergillosis, 14 patients (54%) died. However, 5 of 10 patients (50%) with presumed pulmonary aspergillosis, 3 of 9 patients (33%) with probable pulmonary aspergillosis, 1 of 2 patients (50%) with definite pulmonary aspergillosis, and 3 of 5 patients (60%) with disseminated aspergillosis responded to antifungals and adjuvant interferon‐γ‐1b.CONCLUSIONSRecombinant interferon‐γ‐1b was tolerated without serious adverse reactions in HSCT recipients. A large, prospective, randomized study will be needed to evaluate the efficacy of this cytokine in high‐risk HSCT recipients who have invasive mycoses. Cancer 2005. © 2005 American Cancer Society.