bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Individual Psychological Intervention in Chinese Women With Gynecologic Malignancy: A Randomized Controlled Trial
Authors: Chan Y.M. , Lee Peter W.H. , Fong Daniel Y.T. , Fung Amy S.M. , Wu Lina Y.F. , Choi Alice Y.Y. , Ng T.Y. , Ngan Hextan Y.S. , Wong L.C. 
Published: June 2005

Purpose To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated. Patients and Methods Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and randomly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy. A set of fixed-choice, self-report questionnaires assessing the patients' psychological status, quality of life, and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months. Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model. Multivariable analyses were performed to examine the effects of confounding factors. Results One hundred fifty-five patients participated in the trial. There were no statistically significant differences between the two groups at baseline. There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups. No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis. Psychological intervention had no significant effects on the psychosocial parameters. Conclusion Routine use of psychological therapies as given in our format has no significant effect on the patients' quality of life and psychological status.
Phase I and Pharmacokinetic Study of LY293111, an Orally Bioavailable LTB4 Receptor Antagonist, in Patients With Advanced Solid Tumors
Authors: Schwartz Gary K. , Weitzman Aaron , O'Reilly Eileen , Brail Les , de Alwis Dinesh P. , Cleverly Ann , Barile-Thiem Barbara , Vinciguerra Vincent , Budman Daniel R. 
Published: June 2005

Purpose LY293111, a novel diaryl ether carboxylic acid derivative, is a potent and selective inhibitor of the lipoxygenase pathway either directly through 5′-lipoxygenase or via antagonism of the leukotriene B4 (LTB4) receptor. More recently it has been determined to have peroxisome proliferator activated receptor-gamma agonist (PPARγ) activity. LY293111 has antineoplastic activity in a variety of preclinical models. The tolerability and pharmacokinetics of LY293111 administered continuously, by mouth, BID for repeat cycles of 21 days was evaluated. Patients and Methods Thirty-eight patients with advanced solid tumors were treated at five dose levels (200 to 800 mg BID) for a total of 102 cycles. Results The most common toxicity was diarrhea (76%). One patient at 600 mg BID (n = 11) and two at 800 mg BID (n = 8), experienced dose-limiting grade 3 diarrhea. Dose reductions and/or delays were infrequent. Increases in steady-state maximum plasma concentration (Cmax,ss) and area under the steady-state plasma concentration time curve 0 to 12 hours (AUCτ,ss) on day 8 could be considered to be dose-proportional over the four-fold-dose range. Interpatient variability in Cmax,ss and AUCτ,ss was estimated to be 65% and 71% respectively. There was a small increase in AUC (1.37; 90% CI, 0.85 to 2.21) between single and multiple doses. Two patients with progressive chondrosarcoma and melanoma had stable disease lasting approximately 336 and 168 days, respectively. Conclusion LY293111 can be administered safely by continuous oral therapy with mild toxicities. Diarrhea is dose-limiting. The recommended phase II dose will be 600 mg BID. The steady-state concentrations in humans exceed relevant levels observed in preclinical models.
Thalidomide Downregulates Angiogenic Genes in Bone Marrow Endothelial Cells of Patients With Active Multiple Myeloma
Authors: Vacca Angelo , Scavelli Claudio , Montefusco Vittorio , Di Pietro Giulia , Neri Antonino , Mattioli Michela , Bicciato Silvio , Nico Beatrice , Ribatti Domenico , Dammacco Franco , Corradini Paolo 
Published: June 2005

PurposeTo study the antiangiogenic effect of thalidomide.Patients and MethodsThe expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.ResultsThalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.ConclusionInhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.
Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell’Italia Meridionale
Authors: Colucci Giuseppe , Gebbia Vittorio , Paoletti Giancarlo , Giuliani Francesco , Caruso Michele , Gebbia Nicola , Cartenì Giacomo , Agostara Biagio , Pezzella Giuseppe , Manzione Luigi , Borsellino Nicola , Misino Andrea , Romito Sante , Durini Ernesto , Cordio Stefano , Di Seri Marisa , Lopez Massimo , Maiello Evaristo 
Published: June 2005

Purpose We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. Patients and Methods A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m2 on day 1 with LV5FU2 regimen). Results One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. Conclusion There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.
Phase II and Tumor Pharmacodynamic Study of Gefitinib in Patients with Advanced Breast Cancer
Authors: Baselga José , Albanell Joan , Ruiz Amparo , Lluch Ana , Gascón Pere , Guillém Vicente , González Sonia , Sauleda Silvia , Marimón Irene , Tabernero Josep M. , Koehler Maria T. , Rojo Federico 
Published: June 2005

Purpose To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer. Methods In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue. Results Of 31 assessable patients, 12 (38.7%) had stable disease, including 3 (9.7%) with recurrent breast cancer that stabilized for ≥ 6 months. No complete or partial responses were observed. Pretreatment tumor samples were available in all patients. In addition, paired baseline and on-treatment (day 28) assessable skin and tumor biopsies were available in 27 and 16 patients, respectively. Sequential immunohistochemical studies in skin and tumor biopsies demonstrated complete inhibition of epidermal growth factor receptor (EGFR) phosphorylation in both healthy and malignant tissues. The downstream consequences of receptor blockade were distinct in skin and tumor samples: while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the activated form of Akt in the tumors. Conclusion This study demonstrates a good correlation between the degree of inhibition of EGFR in skin and in breast tumors. The lack of significant clinical activity of gefitinib in our study population is not due to lack of receptor inhibition in these tumors but rather to lack of EGFR dependence in the tested population.
Adjuvant Cisplatin Plus Methotrexate Versus Methotrexate, Vinblastine, Epirubicin, and Cisplatin in Locally Advanced Bladder Cancer: Results of a Randomized, Multicenter, Phase III Trial (AUO-AB 05/95)
Authors: Lehmann Jan , Retz Margitta , Wiemers Christina , Beck Joachim , Thüroff Joachim , Weining Christoph , Albers Peter , Frohneberg Detlef , Becker Tanja , Funke Peter-Jörg , Walz Peter , Langbein Sigrun , Reiher Frank , Schiller Matthias , Miller Kurt , Roth Stephan , Kälble Tilman , Sternberg Donald , Wellek Stefan , Stöckle Michael 
Published: June 2005

Purpose Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy. Patients and Methods A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm2 on day 1 and methotrexate 40 mg/qm2 on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm2 on days 1, 15, and 22, vinblastine 3 mg/qm2 on days 2, 15, and 22, epirubicin 45 mg/qm2 on day 2, and cisplatin 70 mg/qm2 on day 2 of a 28-day cycle (M-VEC). Results The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (α = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates ± SE) for CM versus M-VEC were 46.3% ± 4.6% v 48.8% ± 4.5%, 52.0% ± 4.6% v 52.3% ± 4.8%, and 46.1% ± 4.3% v 45.1% ± 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001). Conclusion CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.
Regulation of ghrelin secretion by somatostatin analogs in rats
Authors: Silva Antonio P , Bethmann Kerstin , Raulf Friedrich , Schmid Herbert A 
Published: June 2005

Objective: Ghrelin is a hormone present in the plasma in two forms: octanoylated and des-octanoylated ghrelin. In pathophysiological conditions such as Prader–Willi syndrome and ghrelinoma, elevated ghrelin plasma levels are associated with pathological obesity. Clinical studies have shown that somatostatin downregulates ghrelin plasma levels in healthy volunteers. The aim of this study was to investigate the effects of two somatostatin analogues, SOM230 and octreotide, on ghrelin secretion in rats.
Methods: Ghrelin secretion was either unstimulated or stimulated by overnight fasting. Treatment with SOM230 and octreotide was either acute (s.c. injection 1 h before blood sampling) or prolonged (continuous s.c. infusion via 14-day osmotic minipumps).
Results: Acute treatment with octreotide dose-dependently inhibited unstimulated and stimulated secretion of total and active ghrelin. SOM230 (30 μg/kg) inhibited active ghrelin in fasted rats. Lower doses had no effect. After 7 days of treatment, active ghrelin was strongly inhibited by both compounds in fasted animals, with a stronger effect for octreotide. Lower inhibition was achieved in fed rats. After 14 days, the inhibition with octreotide in fasted rats was lower and SOM230 had no effect. Somatostatin receptor expression analysis in the rat glandular stomach revealed a predominant sst1 and sst2 expression, low expression of sst3 and sst4, and hardly detectable sst5 mRNA expression.
Conclusions: Somatostatin analogues may be useful for the inhibition of physiologically elevated ghrelin plasma levels. This inhibition appears to be mediated by sst2 receptors in the rat, and desensitizes after 14 days of treatment.
Adult height of prepubertal short children born small for gestational age treated with GH
Authors: Rosilio Myriam , Carel Jean-Claude , Ecosse Emmanuel , Chaussainon Jean-Louis , _ _ 
Published: June 2005

Objective: Human GH (hGH) treatment leads to catch-up growth in children with short stature born small for gestational age (SGA). However, long-term efficacy and safety results in this patient group remain scarce. The present study assessed the efficacy and safety of late childhood treatment with biosynthetic hGH (Humatrope) in a group of short children born SGA (height <−2 standard deviation scores (SDS)).
Design: Patients in this open-label, Phase III, multicenter study received a daily hGH dose of 0.067 mg/kg for 2 years, and then received no treatment for the following 2 years. After the fourth year on study, patients whose height had decreased more than 0.5 SDS but who still showed growth potential based on bone age were allowed to resume treatment until they reached adult height.
Methods: Height gain SDS was assessed for 11 girls and 24 boys (mean age±s.d. 9.6±0.9 years) at the end of the 2 years of hGH treatment, during the subsequent 2-year off-treatment period, and upon reaching adult height.
Results: At the end of the initial 2-year treatment period, 83% of patients had reached a height within the normal range, with a mean increase in height SDS vs baseline of 1.3±0.3 (P <0.001). Adult heights (n = 20) were within the normal range for 50% of patients, and mean height gain from baseline was statistically significant (0.7±0.8 SDS, P <0.001). Fasting glucose and glycosylated hemoglobin levels were not significantly modified during treatment.
Conclusions: High-dose hGH treatment for a minimum of 2 years in short children born SGA was well tolerated and resulted in a significant increase in adolescent and adult height.
Mutation analysis of the MCHR1 gene in human obesity
Authors: Wermter Anne-Kathrin , Reichwald Kathrin , Büch Thomas , Geller Frank , Platzer Cornelia , Huse Klaus , Hess Claudia , Remschmidt Helmut , Gudermann Thomas , Preibisch Gerald , Siegfried Wolfgang , Goldschmidt Hans-Peter , Li Wei-Dong , Price R Arlen , Biebermann Heike , Krude Heiko , Vollmert Caren , Wichmann H-Erich , Illig Thomas , Sørensen Thorkild I A , Astrup Arne , Larsen Lesli Hingstrup , Pedersen Oluf , Eberlé Delphine , Clément Karine , Blundell John , Wabitsch Martin , Schäfer Helmut , Platzer Matthias , Hinney Anke , Hebebrand Johannes 
Published: June 2005

Objective: The importance of the melanin-concentrating hormone (MCH) system for regulation of energy homeostasis and body weight has been demonstrated in rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human obesity.Design: This consisted of genomic screening of 13.4 kb encompassing theMCHR1in extremely obese German children and adolescents and association analyses for two coding single nucleotide polymorphisms (SNPs). To confirm initial positive association results, additional association studies and transmission disequilibrium tests in further German, Danish, French and American samples were conducted. Selected SNPs were investigated using functionalin vitrostudies and reporter gene assays.Methods: Single-stranded conformation polymorphism analysis, re-sequencing, PCR-restriction fragment length polymorphism analyses, tetra-primer amplification refractory mutation systems, matrix-assisted laser desorption/ionization time of flight mass spectrometry and reporter gene assays were carried out as well as measuring inositol phosphate formation, inhibition of cAMP formation and activation of p42/44 MAP kinase.Results: We identified 11 infrequent variations and two SNPs in theMCHR1coding sequence and 18 SNPs (eight novel) in the flanking sequence. Association and transmission disequilibrium with obesity were detected for several SNPs in independent study groups of German obese children and adolescents and controls. In two German samples, encompassing 4056 and 295 individuals, trends towards association with obesity were detected. Findings in a second epidemiological German sample and in Danish, French and American samples were negative. Functionalin vitrostudies as well as reporter gene assays revealed no significant results.Conclusion: Our initial association ofMCHR1alleles/haplotype detected might be related to juvenile-onset obesity, conditional on a particular genetic and/or environmental background. Alternatively, we could not exclude the possibility that the initially detected association represented a false positive finding.
Sympatho-vagal control of heart rate variability in patients treated with suppressive doses of L-thyroxine for thyroid cancer
Authors: Casu Massimo , Cappi Caterina , Patrone Vittoriana , Repetto Eva , Giusti Massimo , Minuto Francesco , Murialdo Giovanni 
Published: June 2005

Objective: This study aimed to analyze the autonomic control of heart rate variability (HRV) in subjects receiving chronic l-thyroxine (l-T4) treatment after total thyroidectomy and 131I therapy for differentiated thyroid carcinoma.
Methods: Blood pressure (BP) and sympatho-vagal activity (evaluated by power spectral analysis (PSA) of time-domain parameters of HRV) were studied in clinostatism and after orthostatism in 24 healthy controls, and in 12 patients taking l-T4 (125–200 μg/day) to maintain serum TSH levels at <0.01 μIU/ml. The study of HRV by PSA is a non-invasive method of analyzing sympatho-vagal control of HRV by quantifying high-frequency (HF) (0.15–0.4 Hz) and low-frequency (LF) (0.04–0.15 Hz) powers.
Results: Patients on L-T4 treatment had undetectable TSH levels, serum free T4 (fT4) above the normal range or at the upper limit in one case, and normal free tri-iodothyronine (fT3) levels. Heart rate and R–R intervals were not different in the two groups, both in clinostatism and in ortostatism. Systolic and mean BP were higher in patients than in controls and were inversely correlated with actual serum fT4 levels. During clinostatism, thyroid patients showed significantly lower LF power (P = 0.035), LF/(LF + HF) (P = 0.008) and LF/HF (P = 0.01) than controls. When patients moved from lying to standing, there was a significantly different decrease in orthostatic LF power (P = 0.001), LF/(LF + HF) (P = 0.044) and LF/HF (P = 0.047) versus controls.
Conclusions: Changes in autonomic control of HRV, characterized by decreased sympathetic activity and impaired sympatho-vagal balance with preserved vagal tone, are detectable in patients with hyperthyroxinemia due to suppressive l-T4 therapy and increased systolic and mean, but not diastolic, BP.
Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern
Authors: Natalucci G , Riedl S , Gleiss A , Zidek T , Frisch H 
Published: June 2005

Objective: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utilization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail.
Design: 24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m2) and compared with GH, insulin and glucose levels.
Methods: Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated.
Results: An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels.
Conclusions: This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition, GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.