bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data from necropsy studies and in vitro tissue studies lead to a model for allometric scaling of basal metabolic rate
Authors: Painter Page R 
Published: September 2005

Abstract

Background
The basal metabolic rate (BMR) of a mammal of mass M is commonly described by the power function αM

β
where α and β are constants determined by linear regression of the logarithm of BMR on the logarithm of M (i. e., β is the slope and α is the intercept in regression analysis). Since Kleiber's demonstration that, for 13 measurements of BMR, the logarithm of BMR is closely approximated by a straight line with slope 0.75, it has often been assumed that the value of β is exactly 3/4 (Kleiber's law).

Results
For two large collections of BMR data (n = 391 and n = 619 species), the logarithm of BMR is not a linear function of the logarithm of M but is a function with increasing slope as M increases. The increasing slope is explained by a multi-compartment model incorporating three factors: 1) scaling of brain tissue and the tissues that form the surface epithelium of the skin and gastrointestinal tract, 2) scaling of tissues such as muscle that scale approximately proportionally to body mass, and 3) allometric scaling of the metabolic rate per unit cell mass. The model predicts that the scaling exponent for small mammals (body weight < 0.2 kg) should be less than the exponent for large mammals (> 10 kg). For the simplest multi-compartment model, the two-compartment model, predictions are shown to be consistent with results of analysis using regression models that are first-order and second-order polynomials of log(M). The two-compartment model fits BMR data significantly better than Kleiber's law does.

Conclusion
The F test for reduction of variance shows that the simplest multi-compartment allometric model, the two-compartment model, fits BMR data significantly better than Kleiber's law does and explains the upward curvature observed in the BMR.
Mutations affecting cleavage at the p10-capsid protease cleavage site block Rous sarcoma virus replication
Authors: Vana Marcy L , Chen Aiping , Boross Peter , Weber Irene , Colman Dalbinder , Barklis Eric , Leis Jonathan 
Published: September 2005

Abstract
A series of amino acid substitutions (M239F, M239G, P240F, V241G) were placed in the p10-CA protease cleavage site (VVAM*PVVI) to change the rate of cleavage of the junction. The effects of these substitutions on p10-CA cleavage by RSV PR were confirmed by measuring the kinetics of cleavage of model peptide substrates containing the wild type and mutant p10-CA sites. The effects of these substitutions on processing of the Gag polyprotein were determined by labeling Gag transfected COS-1 cells with 35S-Met and -Cys, and immunoprecipitation of Gag and its cleavage products from the media and lysate fractions. All substitutions except M239F caused decreases in detectable Gag processing and subsequent release from cells. Several of the mutants also caused defects in production of the three CA proteins. The p10-CA mutations were subcloned into an RSV proviral vector (RCAN) and introduced into a chick embryo fibroblast cell line (DF-1). All of the mutations except M239F blocked RSV replication. In addition, the effects of the M239F and M239G substitutions on the morphology of released virus particles were examined by electron microscopy. While the M239F particles appeared similar to wild type particles, M239G particles contained cores that were large and misshapen. These results suggest that mutations affecting cleavage at the p10-CA protease cleavage site block RSV replication and can have a negative impact on virus particle morphology.
Ethnopharmacological survey of different uses of seven medicinal plants from Mali, (West Africa) in the regions Doila, Kolokani and Siby
Authors: Togola Adiaratou , Diallo Drissa , Dembélé Seydou , Barsett Hilde , Paulsen Berit Smestad 
Published: September 2005

Abstract
An ethnopharmacological survey was carried out to collect information on the use of seven medicinal plants in rural areas in the nearby regions of Bamako, Mali. The plants were Opilia celtidifolia, Anthocleista djalonensis, Erythrina senegalensis, Heliotropium indicum, Trichilia emetica, Piliostigma thonningii and Cochlospermum tinctorium

About 50 medical indications were reported for the use of these plants in traditional medicine. The most frequent ailments reported were malaria, abdominal pain and dermatitis. The highest number of usages was reported for the treatment of malaria (22%). The majority of the remedies were prepared from freshly collected plant material from the wild and from a single species only. They were mainly taken orally, but some applications were prepared with a mixture of plants or ingredients such as honey, sugar, salt, ginger and pepper. Decoction of the leaves was the main form of preparation (65%) and leaf powder was mostly used for the preparation of infusions (13%). The part of the plants most frequently used was the leaves. There was a high degree of informant consensus for the species and their medicinal indications between the healers interviewed.
The results of this study showed that people are still dependent on medicinal plants in these rural areas of Mali.
Targeted therapy against Bcl-2-related proteins in breast cancer cells
Authors: Emi Manabu , Kim Ryungsa , Tanabe Kazuaki , Uchida Yoko , Toge Tetsuya 
Published: September 2005

Abstract
Introduction
Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy.

Methods
Four human breast cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the antitumor effect was assessed in vivo by the success of xenograft transplantation into athymic mice.

Results
Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a sequence-specific decrease in protein expression, compared with controls. Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, which was attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to a smaller extent, are major determinants of chemosensitivity in breast cancer cells.

Conclusion
Targeted therapy against Bcl-2 protein with the use of AS ODNs might enhance the effects of chemotherapy in patients with breast cancer.
Pretreatment Quality of Life and Functional Status Assessment Significantly Predict Survival of Elderly Patients With Advanced Non—Small-Cell Lung Cancer Receiving Chemotherapy: A Prognostic Analysis of the Multicenter Italian Lung Cancer in the Elderly Study
Authors: Maione Paolo , Perrone Francesco , Gallo Ciro , Manzione Luigi , Piantedosi FrancoVito , Barbera Santi , Cigolari Silvio , Rosetti Francesco , Piazza Elena , Robbiati Sergio Federico , Bertetto Oscar , Novello Silvia , Migliorino Maria Rita , Favaretto Adolfo , Spatafora Mario , Ferraù Francesco , Frontini Luciano , Bearz Alessandra , Repetto Lazzaro , Gridelli Cesare 
Published: September 2005

Purpose To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non—small-cell lung cancer treated with chemotherapy. Patients and Methods Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. Results Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. Conclusions Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non—small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.
Darbepoetin Alfa for the Treatment of Chemotherapy-Induced Anemia: Disease Progression and Survival Analysis From Four Randomized, Double-Blind, Placebo-Controlled Trials
Authors: Hedenus Michael , Vansteenkiste Johan , Kotasek Dusan , Austin Matthew , Amado Rafael G. 
Published: September 2005

Purpose To determine the effect of darbepoetin alfa (DA) on progression-free survival (PFS) and overall survival (OS) in patients with chemotherapy-induced anemia (CIA). Patients and Methods Two 16-week randomized, double-blind, placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer (n = 314) or lymphoproliferative malignancies (LPMs; n = 344) undergoing chemotherapy were analyzed with prospectively defined long-term PFS and OS end points. Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding, double-blind, placebo-controlled studies in anemic patients with multiple tumor types (n = 405) and LPMs (n = 66). Results Median follow-up is 15.8 months (lung cancer) and 32.6 months (LPM). Median duration of PFS was comparable between DA and placebo: 5.1 months (95% CI, 4.1 to 6.9 months) versus 4.4 months (95% CI, 3.7 to 5.3 months) for lung cancer and 14.2 months (95% CI, 12.2 to 17.5 months) versus 15.9 months (95% CI, 13.1 to 19.0 months) for LPMs. The estimated hazard ratio (HR) of death related to DA use for lung cancer was 0.77 (95% CI, 0.59 to 1.01) and 1.26 (95% CI, 0.92 to 1.71) for LPMs. In the pooled analyses of all four studies (n = 1,129), no differences in PFS or OS were observed between DA and placebo (HR = 0.92; 95% CI, 0.78 to 1.07; and HR = 0.95; 95% CI, 0.78 to 1.16, respectively). Conclusion Treatment with DA does not seem to influence PFS or OS in patients with CIA. Prospective, randomized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types.
Phase II to III Study Comparing Doxorubicin and Docetaxel With Fluorouracil, Doxorubicin, and Cyclophosphamide As First-Line Chemotherapy in Patients With Metastatic Breast Cancer: Results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre
Authors: Bontenbal Marijke , Creemers Geert-Jan , Braun Hans J. , de Boer Auke C. , Janssen Jos Th. , Leys Rieneke B. , Ruit Jan B. , Goey Swan Hoo , van der Velden Paul C. , Kerkhofs Leon G. , Schothorst Kristel L. , Schmitz Paul I. , Bokma Hansje J. , Verweij Jaap , Seynaeve Caroline 
Published: September 2005

Purpose To compare the efficacy and safety of doxorubicin and docetaxel (AT) with fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients (n = 216) were randomly assigned to either AT (doxorubicin 50 mg/m2 and docetaxel 75 mg/m2) or FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); both regimens were administered on day 1, every 3 weeks. Results A median number of six cycles was delivered in both arms, with a median relative dose-intensity of more than 98%. Median time to progression (TTP) and median overall survival (OS) were significantly longer for patients on AT compared with FAC (TTP: 8.0 v 6.6 months, respectively; P = .004; and OS: 22.6 v 16.2 months, respectively; P = .019). The overall response rate (ORR) was significantly higher in patients on AT compared with FAC (58% v 37%, respectively; P = .003). The ORR on AT was also higher in patients with visceral disease compared with FAC patients with visceral disease (59% v 36%, respectively; P = .003). There were no differences in grade 3 to 4 neutropenia and infections (AT 89% v FAC 84% and AT 12% v FAC 9%, respectively). Neutropenic fever was more common in AT-treated patients than FAC-treated patients (33% v 9%, respectively; P < .001). Grade 3 to 4 nonhematologic toxicity was infrequent in both arms. Congestive heart failure was observed in 3% and 6% of patients on AT and FAC, respectively. Conclusion In this phase II to III study, AT resulted in a significantly longer TTP and OS and a higher objective ORR than FAC. First-line AT is a valid treatment option for patients with MBC.
Phase I Trial of Temozolomide Plus O6-Benzylguanine for Patients With Recurrent or Progressive Malignant Glioma
Authors: Quinn Jennifer A. , Desjardins Annick , Weingart Jon , Brem Henry , Dolan M. Eileen , Delaney Shannon M. , Vredenburgh James , Rich Jeremy , Friedman Allan H. , Reardon David A. , Sampson John H. , Pegg Anthony E. , Moschel Robert C. , Birch Robert , McLendon Roger E. , Provenzale James M. , Gururangan Sridharan , Dancey Janet E. , Maxwell Jill , Tourt-Uhlig Sandra , Herndon James E. , Bigner Darell D. , Friedman Henry S. 
Published: September 2005

Purpose We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. Patients and Methods For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. Results The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. Conclusion This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.
Comparison of Outcomes of Phase II Studies and Subsequent Randomized Control Studies Using Identical Chemotherapeutic Regimens
Authors: Zia Mohammad I. , Siu Lillian L. , Pond Greg R. , Chen Eric X. 
Published: September 2005

Purpose To determine whether promising results from phase II studies could be reproduced in phase III studies, and to examine which characteristics of phase II studies might be of predictive value for subsequent phase III studies. Methods We searched for all phase III studies of chemotherapy in advanced solid malignancies, published in the English language literature from July 1998 to June 2003. Each phase III study was reviewed to identify preceding phase II studies. Phase II and phase III studies included in this analysis must have used identical regimens. Data were extracted from both phase II and phase III studies. Results Of 181 phase III studies identified, 43 used therapeutic regimens identical to those in 49 preceding phase II studies. Twelve phase III studies (28%) were “positive.” The vast majority (81%) of phase III studies have lower response rates than preceding phase II studies, with a mean difference of 12.9% among all studies analyzed. None of the phase II study characteristics evaluated significantly predicted for “positive” phase III studies, but the sample size of phase II studies demonstrated a trend toward being predictive (P = .083). Conclusion Promising results from phase II studies frequently do not translate into “positive” phase III studies. Response rates in most phase III studies are lower than those in preceding phase II studies.
Prognostic Value of Extracapsular Tumor Spread for Locoregional Control in Premenopausal Patients With Node-Positive Breast Cancer Treated With Classical Cyclophosphamide, Methotrexate, and Fluorouracil: Long-Term Observations From International Breast Cancer Study Group Trial VI
Authors: Gruber Günther , Bonetti Marco , Nasi M. Laura , Price Karen N. , Castiglione-Gertsch Monica , Rudenstam Carl-Magnus , Holmberg Stig B. , Lindtner Jurij , Golouh Rastko , Collins John , Crivellari Diana , Carbone Antonino , Thürlimann Beat , Simoncini Edda , Fey Martin F. , Gelber Richard D. , Coates Alan S. , Goldhirsch Aron 
Published: September 2005

Purpose We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+). Patients and Methods We randomized 1,475 premenopausal women with node-positive breast cancer to three, six, or nine courses of “classical” CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years. Results In univariate analyses, ECS was associated with worse disease-free survival (DFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% CI, 1.34 to 1.93; P < .0001; OS: 1.67; 95% CI, 1.34 to 2.08; P < .0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate ± distant failure (LRF ± distant failure) within 10 years was estimated at 19% (± 2%) without ECS, versus 27% (± 2%) with ECS. The difference was statistically significant in univariate analyses, but not after adjusting for the number of positive nodes. No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy. Conclusion Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance.
Paroxetine Is an Effective Treatment for Hot Flashes: Results From a Prospective Randomized Clinical Trial
Authors: Stearns Vered , Slack Rebecca , Greep Nancy , Henry-Tilman Ronda , Osborne Michael , Bunnell Craig , Ullmer Lynda , Gallagher Ann , Cullen Jennifer , Gehan Edmund , Hayes Daniel F , Isaacs Claudine 
Published: September 2005

Purpose In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters. Patients and Methods Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9. Results 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01). Conclusion Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.
Population-Based Analysis of Prognostic Factors and Survival in Familial Melanoma
Authors: Florell Scott R. , Boucher Kenneth M. , Garibotti Gilda , Astle John , Kerber Richard , Mineau Geraldine , Wiggins Charles , Noyes R. Dirk , Tsodikov Alexander , Cannon-Albright Lisa A. , Zone John J. , Samlowski Wolfram E. , Leachman Sancy A. 
Published: September 2005

Purpose Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. Patients and Methods This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. Results Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). Conclusion These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.