bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of exercise and nutritional counseling in women with polycystic ovary syndrome
Authors: Bruner Brenda , Chad Karen , Chizen Donna 
Published: August 2006

This pilot study assessed the effects of exercise and nutritional counseling on hormonal, menstrual, and reproductive function in women with polycystic ovary syndrome (PCOS). Twelve females with a clinical, biochemical, and ultrasonographic diagnosis of PCOS were randomly assigned to endurance and resistance exercise plus nutritional counseling (EN) or nutritional counseling only (N) for a period of 12 weeks. Anthropometry, resting metabolic rate (RMR), selected hormones, and ovarian follicle population were measured pre and post-intervention. Following the 12 week intervention, greater decreases in sum of 2 skinfolds (p = 0.002) and a greater increase in estimated VO2 max (p = 0.017) occurred in the exercise group. Significant decreases in waist girth (p = 0.001) and insulin levels (p = 0.03) occurred in both groups. Hormonal changes were not statistically significant; however, a trend towards an improved hormonal profile, specifically sex-hormone binding globulin (EN, 39% increase; N, 8% increase) and lutenizing hormone : follicle-stimulating hormone (LH:FSH) (EN, 9% decrease; N, 27% decrease) occurred in the absence of weight loss. These findings suggest exercise and nutritional counseling may benefit the metabolic and reproductive abnormalities associated with PCOS.
Early effects of spinal cord transection on skeletal muscle properties
Authors: Kelley Melissa D. , Nim Satra , Rousseau Guy , Fowles Jonathon R. , Murphy René J.L. 
Published: August 2006

Modulation of β-adrenergic receptor (β-AR) activity affects muscle mass and could have a role in the reduction of muscle mass observed following spinal cord transection (Tx). The aims of this study were to examine the early acute effects of Tx on muscle mass, total and myofibrillar protein concentrations, cytochrome c oxidase activity, and β-AR density of skeletal muscle, to ascertain if any change in muscle properties could be related to β-AR signalling events. Female Sprague–Dawley rats (n = 33; ~255 g) were randomly assigned to 4 experimental groups: control 4 d, control 8 d, Tx 4 d, and Tx 8 d. A complete Tx was performed surgically at the T10 cord level. Compared with controls, muscle mass and muscle – body mass ratios decreased significantly following Tx, with no significant change observed in total and myofibrillar protein concentrations. Spinal cord Tx also resulted in a significant decrease in plantaris cytochrome c oxidase activity by 24% at Tx 4 d and 28% at Tx 8 d (p < 0.05). β-AR density of the lateral gastrocnemius was unchanged; however, the β-AR density of the forelimb triceps brachii m. was found to increase after Tx. Our results suggest that changes in muscle mass and cytochrome c oxidase activity rapidly occur after Tx and do not appear to be related to changes in β-AR density.
Effect of differences in post-exercise lactate accumulation in athletes’ haemodynamics
Authors: Crisafulli Antonio , Tocco Filippo , Pittau Gianluigi , Lorrai Luigi , Porru Cristina , Salis Enrico , Pagliaro Pasquale , Melis Franco , Concu Alberto 
Published: August 2006

To verify the relationship between exercise intensity and post-exercise haemodynamics, we studied haemodynamic and lactate responses during 10 min following 3 bicycle tests. Two tests were performed for 3 min at 70% and 130% of the workload corresponding to anaerobic threshold (70% Wat and 130% Wat tests), and 1 was performed until exhaustion at 150% of the maximum workload achieved during a previous incremental test (150% Wmax test). During the recovery period after the 150% Wmax test we observed the highest increases in blood lactate with respect to the baseline: at the 9th minute of recovery lactate concentration increased by +9.3 ± 2.7, +6.4 ± 3.1, and +1.1 ± 0.9 mmol·L–1 in the 150% Wmax (p > 0.05 with respect to the other protocol sessions), 130% Wat, and 70% Wat tests, respectively. We also observed greater reductions in cardiac pre-load and systemic vascular resistance in the 150% Wmax test than in the 130% Wat and 70% Wat tests. However, the cardiac output response successfully faced the increased vasodilatation occurring during 150% Wmax test so that changes in mean blood pressure were similar in the 3 test conditions. This study shows that exercises that yielded different lactate concentrations also led to greater vasodilatation. Nevertheless, mechanisms controlling the cardiovascular apparatus successfully prevented a drop in blood pressure in spite of the cardiovascular stress.
In vitro Drug Response and Molecular Markers Associated with Drug Resistance in Malignant Gliomas
Authors: Fruehauf John P. , Brem Henry , Brem Steven , Sloan Andrew , Barger Geoffrey , Huang Weidong , Parker Ricardo 
Published: August 2006

Abstract
Purpose: Drug resistance in malignant gliomas contributes to poor clinical outcomes. We determined the in vitro drug response profiles for 478 biopsy specimens from patients with the following malignant glial histologies: astrocytoma (n = 71), anaplastic astrocytoma (n = 39), glioblastoma multiforme (n = 259), oligodendroglioma (n = 40), and glioma (n = 69).
Experimental Design: Samples were tested for drug resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, dacarbazine, paclitaxel, vincristine, and irinotecan. Biomarkers associated with drug resistance were detected by immunohistochemistry, including multidrug resistance gene-1, glutathione S-transferase π (GSTP1), O6-methylguanine-DNA methyltransferase (MGMT), and mutant p53.
Results: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance.
Conclusions: Assessment of in vitro drug response and profiles of relevant tumor-associated biomarkers may assist the clinician in stratifying patient treatment regimens.
Prognosis and Gene Expression Profiling of 20q13-Amplified Breast Cancers
Authors: Ginestier Christophe , Cervera Nathalie , Finetti Pascal , Esteyries Séverine , Esterni Benjamin , Adélaïde José , Xerri Luc , Viens Patrice , Jacquemier Jocelyne , Charafe-Jauffret Emmanuelle , Chaffanet Max , Birnbaum Daniel , Bertucci François 
Published: August 2006

AbstractPurpose: Amplification of chromosomal region 20q13 occurs in breast cancer but remains poorly characterized.Experimental Design: To establish the frequency of 20q13 amplification and select the amplified cases to be studied, we used fluorescence in situ hybridization of bacterial artificial chromosome probes for three 20q13 loci (MYBL2, STK6, ZNF217) on sections of tissue microarrays containing 466 primary carcinoma samples. We used Affymetryx whole-genome DNA microarrays to establish the gene expression profiles of 20q13-amplified tumors and quantitative reverse transcription-PCR to validate the results.Results: We found 36 (8%) 20q13-amplified samples. They were distributed in two types: type 1 tumors showed ZNF217 amplification only, whereas type 2 tumors showed amplification at two or three loci. Examination of the histoclinical features of the amplified tumors showed two strikingly opposite data. First, type 1 tumors were more frequently lymph node–negative tumors but were paradoxically associated with a poor prognosis. Second, type 2 tumors were more frequently lymph node–positive tumors but were paradoxically associated with a good prognosis. Type 1 and type 2 showed different gene expression profiles. No 20q13 gene could be associated with type 1 amplification, whereas several 20q13 genes were overexpressed in type 2 tumors.Conclusions: Our results suggest that amplified tumors of types 1 and 2 are two distinct entities resulting from two different mechanisms and associated to different prognosis.
Increased Bioavailability of Intravenous Versus Oral CI-1033, a Pan erbB Tyrosine Kinase Inhibitor: Results of a Phase I Pharmacokinetic Study
Authors: Simon George R. , Garrett Christopher R. , Olson Stephen C. , Langevin Michael , Eiseman Irene A. , Mahany John J. , Williams Charles C. , Lush Richard , Daud Adil , Munster Pamela , Chiappori Alberto , Fishman Mayer , Bepler Gerold , Lenehan Peter F. , Sullivan Daniel M. 
Published: August 2006

Abstract
Purpose: In phase I studies with oral CI-1033, dose-limiting toxicities were primarily gastrointestinal, supporting the exploration of i.v. dosing to achieve optimal drug exposures by increasing bioavailability.
Experimental Design: Fifty-three patients with advanced nonhematologic malignancies received i.v. CI-1033 via 30-minute infusions (10-500 mg) on a thrice-weekly schedule. Pharmacokinetic samples were collected on days 1 and 8 and evaluated using noncompartmental analysis.
Results: Dose levels evaluated were 10, 20, 30, 45, 67.5, 100, 150, 225, 337.5, and 500 mg. The maximum administered dose was 500 mg, whereas the maximum tolerated dose was 225 mg. The most common treatment-related grade 1 to 2 adverse events were rashes (38% of patients), nausea (17%), vomiting (17%), stomatitis (14%), and diarrhea (13%). Most common grade 3 adverse events were hypersensitivity reactions (7.5%), rashes (3.8%), and diarrhea (3.8%). No grade 4 toxicities were observed. Ten of the 53 (19%) patients had disease stabilization at their first efficacy evaluation visit (including two with minor responses). A 5- to 10-fold increase in i.v. Cmax was noted with a 3-fold increase in AUC compared with oral CI-1033 at equivalent doses. Treatment-related gastrointestinal adverse events were notably less frequent with this i.v. regimen.
Conclusions: CI-1033 was safely given i.v. up to 225 mg/dose on a thrice-weekly schedule, with evidence of antitumor activity. At equivalent doses, the bioavailability of i.v. CI-1033 is thrice that of the oral formulation. Treatment with i.v. CI-1033 is feasible and may be warranted when increased drug exposures are desired.
Cutaneous Melanoma Subtypes Show Different BRAF and NRAS Mutation Frequencies
Authors: Saldanha Gerald , Potter Linda , DaForno Philip , Pringle J. Howard 
Published: August 2006

Abstract
Purpose: BRAF mutations are present in two thirds of cutaneous melanomas and many of the rest have NRAS mutations. However, cutaneous melanoma is a heterogeneous disease with many clinicopathologic subtypes. Of these, the majority fits into four categories: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma (ALM). Thus far, there is very limited data combining BRAF and NRAS mutation analysis to explore differences between cutaneous melanoma subtypes. The aim of this study was to address this issue.
Experimental Design: The frequency of BRAF and NRAS hotspot mutations, in exons 15 and 2, respectively, was assessed in 59 cutaneous melanomas comprising superficial spreading, nodular, lentigo maligna, and ALM using single-strand conformational polymorphism and RFLP-PCR analysis.
Results: Only 2 of 21 (9.5%) ALM showed BRAF exon 15 mutation compared with 9 of 14 (64.3%) superficial spreading malignant melanomas, 4 of 11 (36.4%) nodular melanomas, and 7 of 13 (53.4%) lentigo maligna melanomas (P &lt; 0.01). However, our key finding is that the combined analysis of BRAF exon 15 and NRAS exon 2 showed that there were no significant differences in the overall mutation frequency between subtypes. In particular, 9 of 19 (47.4%) ALM without BRAF exon 15 mutation had an NRAS exon 2 mutation.
Conclusions: We show that the overall BRAF/NRAS frequency in mutation hotspots is not significantly different among cutaneous melanoma subtypes. These data show that mitogen-activated protein kinase pathway activation may be important in all major subtypes of cutaneous melanoma, although the mechanism by which this is achieved varies.
Hypoxia-Inducible Factor-1α Expression Predicts a Poor Response to Primary Chemoendocrine Therapy and Disease-Free Survival in Primary Human Breast Cancer
Authors: Generali Daniele , Berruti Alfredo , Brizzi Maria P. , Campo Leticia , Bonardi Simone , Wigfield Simon , Bersiga Alessandra , Allevi Giovanni , Milani Manuela , Aguggini Sergio , Gandolfi Valeria , Dogliotti Luigi , Bottini Alberto , Harris Adrian L. , Fox Stephen B. 
Published: August 2006

Abstract
Purpose: To investigate the relationship of hypoxia-inducible factor-1α (HIF-1α) tumor expression in predicting the response to epirubicin and disease-free survival (DFS) in patients with breast cancer enrolled in a single institution trial of primary anthracycline and tamoxifen therapy.
Experimental Design: The expression of HIF-1α was assessed by immunohistochemistry in 187 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients postoperatively received four cycles of the four weekly i.v. CMF regimen (cyclophosphamide, methotrexate, and 5-fluorouracil). Patients with estrogen receptor (ER)-positive primary tumors also underwent 5 years of treatment with adjuvant tamoxifen. Carbonic anhydrase IX (CAIX) was also scored as a marker of HIF activity.
Results: Overall response to therapy progressively decreased with increasing tumor HIF-1α (P &lt; 0.05), and HIF-1α was an independent predictor of response (P &lt; 0.048). HIF-1α expression was also associated with a significantly shorter DFS (P &lt; 0.02) in all patients and in ER-positive but not in ER-negative patients. Furthermore, CAIX positivity conferred a significantly shorter DFS (P = 0.02) compared with CAIX-negative tumors in patients with HIF-1α-negative tumors.
Conclusions: HIF-1α expression in patients with breast cancer is a marker of poor therapy response and outcome, especially in ER-positive patients. The combination of two hypoxia markers has greater utility than assessing just one, and patients with hypoxia markers in their tumors may be suitable for administration of drugs that reduce HIF-1α expression and increase oxygen delivery to the tumor bed before starting neoadjuvant therapies.
Hypoxia-Inducible Factor-1 Inhibition in Combination with Temozolomide Treatment Exhibits Robust Antitumor Efficacy In vivo
Authors: Li Leiming , Lin Xiaoyu , Shoemaker Alex R. , Albert Daniel H. , Fesik Stephen W. , Shen Yu 
Published: August 2006

Abstract
Purpose: Inhibiting hypoxia-inducible factor-1 (HIF-1) represents a unique mechanism for cancer therapy. It is conceived that HIF-1 inhibitors may synergize with many classes of cancer therapeutic agents, such as angiogenesis inhibitors and cytotoxic drugs, to achieve a more robust tumor response. However, these hypotheses have not been rigorously tested in tumor models in vivo. The present study was carried out to evaluate the antitumor efficacy of combining HIF-1 inhibition with angiogenesis inhibitors or cytotoxic agents.
Experimental Design: Using a D54MG-derived tumor model that allows knockdown of HIF-1α on doxycycline treatment, we examined the tumor responses to chemotherapeutic agents, including the angiogenesis inhibitor ABT-869 and cytotoxic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide, in the presence or absence of an intact HIF-1 pathway.
Results: Surprisingly, inhibiting HIF-1 in tumors treated with the angiogenesis inhibitor ABT-869 did not produce much added benefit compared with ABT-869 treatment alone, suggesting that the combination of an angiogenesis inhibitor with a HIF-1 inhibitor may not be a robust therapeutic regimen. In contrast, the cytotoxic drug temozolomide, when used in combination with HIF-1α knockdown, exhibited a superadditive and likely synergistic therapeutic effect compared with the monotherapy of either treatment alone in the D54MG glioma model.
Conclusions: Our results show that the DNA alkylating agent temozolomide exhibits robust antitumor efficacy when used in combination with HIF-1 inhibition in D54MG-derived tumors, suggesting that the combination of temozolomide with HIF-1 inhibitors might be an effective regimen for cancer therapy. In addition, our results also show that the RNA interference–based inducible knockdown model can be a valuable platform for further evaluation of the combination treatment of other cancer therapeutics with HIF-1 inhibition.
The Chemokine CCL5 as a Potential Prognostic Factor Predicting Disease Progression in Stage II Breast Cancer Patients
Authors: Yaal-Hahoshen Neora , Shina Sima , Leider-Trejo Leonor , Barnea Itay , Shabtai Esther L. , Azenshtein Elina , Greenberg Iulia , Keydar Iafa , Ben-Baruch Adit 
Published: August 2006

AbstractPurpose: The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers.Experimental Design: The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed.Results: Using Cox proportional hazard models, univariate analysis suggested that, in stage I breast cancer patients, CCL5 was not a significant predictor of disease progression. In contrast, in stage II patients, the expression of CCL5 (CCL5+), the absence of ER-α (ER-α−), and the lack of PR expression (PR−) increased significantly the risk for disease progression (P = 0.0045, 0.0041, and 0.0107, respectively). The prognostic strength of CCL5, as well as of ER-α−, improved by combining them together (CCL5+/ER-α−: P = 0.0001), being highly evident in the stage IIA subgroup [CCL5+/ER-α− (P = 0.0003); ER-α− (P = 0.0315)]. In the stage II group as a whole, the combinations of CCL5−/ER-α+ and CCL5−/PR+ were highly correlated with an improved prognosis. Multivariate analysis indicated that, in stage II patients, ER-α and CCL5 were independent predictors of disease progression.Conclusions: CCL5 could be considered as a biomarker for disease progression in stage II breast cancer patients, with the CCL5+/ER-α− combination providing improved prediction of disease progression, primarily in the stage IIA subgroup.
An In vivo Platform for Translational Drug Development in Pancreatic Cancer
Authors: Rubio-Viqueira Belen , Jimeno Antonio , Cusatis George , Zhang Xianfeng , Iacobuzio-Donahue Christine , Karikari Collins , Shi Chanjusn , Danenberg Kathleen , Danenberg Peter V. , Kuramochi Hidekazu , Tanaka Koji , Singh Sharat , Salimi-Moosavi Hossein , Bouraoud Nadia , Amador Maria L. , Altiok Soner , Kulesza Piotr , Yeo Charles , Messersmith Wells , Eshleman James , Hruban Ralph H. , Maitra Anirban , Hidalgo Manuel 
Published: August 2006

Abstract
Effective development of targeted anticancer agents includes the definition of the optimal biological dose and biomarkers of drug activity. Currently available preclinical models are not optimal to this end. We aimed at generating a model for translational drug development using pancreatic cancer as a prototype. Resected pancreatic cancers from 14 patients were xenografted and expanded in successive groups of nude mice to develop cohorts of tumor-bearing mice suitable for drug therapy in simulated early clinical trials. The xenografted tumors maintain their fundamental genotypic features despite serial passages and recapitulate the genetic heterogeneity of pancreatic cancer. The in vivo platform is useful for integrating drug screening with biomarker discovery. Passages of tumors in successive cohorts of mice do not change their susceptibility to anticancer agents and represent a perpetual live bank, facilitating the application of new technologies that will result in the creation of an integrated stable database of tumor-drug response data and biomarkers.
Induction of Interleukin-6 by Hepatitis C Virus Core Protein in Hepatitis C–Associated Mixed Cryoglobulinemia and B-Cell Non–Hodgkin's Lymphoma
Authors: Feldmann Georg , Nischalke Hans Dieter , Nattermann Jacob , Banas Brigitte , Berg Thomas , Teschendorf Christian , Schmiegel Wolff , Dührsen Ulrich , Halangk Juliane , Iwan Agathe , Sauerbruch Tilman , Caselmann Wolfgang H. , Spengler Ulrich 
Published: August 2006

Abstract
Purpose: Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non–Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL.
Experimental Design: Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA.
Results: HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14+ cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P &lt; 0.05).
Conclusions: Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C–associated MC and B-NHL.