bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group
Authors: Rebbeck Timothy R. , Friebel Tara , Wagner Theresa , Lynch Henry T. , Garber Judy E. , Daly Mary B. , Isaacs Claudine , Olopade Olufunmilayo I. , Neuhausen Susan L. , van ′t Veer Laura , Eeles Rosalind , Evans D. Gareth , Tomlinson Gail , Matloff Ellen , Narod Steven A. , Eisen Andrea , Domchek Susan , Armstrong Katrina , Weber Barbara L. 
Published: October 2005

Purpose Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT. Methods We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years. Results Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96). Conclusion Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers.
Endoscopic Ultrasound–Guided Fine-Needle Aspiration in the Diagnosis and Staging of Lung Cancer and Its Impact on Surgical Staging
Authors: Annema Jouke T. , Versteegh Michel I. , Veseliç Maud , Voigt Pieter , Rabe Klaus F. 
Published: October 2005

Purpose The diagnosis and staging of lung cancer critically depends on surgical procedures. Endoscopic ultrasound (EUS) –guided fine-needle aspiration (FNA) is an accurate, safe, and minimally invasive technique for the analysis of mediastinal lymph nodes (LNs) and can additionally detect tumor invasion (T4) in patients with centrally located tumors. The goal of this study was to assess to what extent EUS-FNA could prevent surgical interventions. Patients and Methods Two hundred forty two consecutive patients with suspected (n = 142) or proven (n = 100) lung cancer and enlarged (> 1 cm) mediastinal LNs at chest computed tomography were scheduled for mediastinoscopy/tomy (94%) or exploratory thoracotomy (6%). Before surgery, all patients underwent EUS-FNA. If EUS-FNA established LN metastases, tumor invasion, or small-cell lung cancer (SCLC), scheduled surgical interventions were cancelled. Surgical-pathologic verification occurred when EUS-FNA did not demonstrate advanced disease. Cancelled surgical interventions because of EUS findings was the primary end point. Results EUS-FNA prevented 70% of scheduled surgical procedures because of the demonstration of LN metastases in non–small-cell lung cancer (52%), tumor invasion (T4) (4%), tumor invasion and LN metastases (5%), SCLC (8%), or benign diagnoses (1%). Sensitivity, specificity, and accuracy for EUS in mediastinal analysis were 91%, 100% and 93%, respectively. No complications were recorded. Conclusion EUS-FNA qualifies as the initial staging procedure of choice for patients with (suspected) lung cancer and enlarged mediastinal LNs. Implementation of EUS-FNA in staging algorithms for lung cancer might reduce the number of surgical staging procedures considerably.
Galectin-1: A Link Between Tumor Hypoxia and Tumor Immune Privilege
Authors: Le Quynh-Thu , Shi Gongyi , Cao Hongbin , Nelson Daniel W. , Wang Yingyun , Chen Eunice Y. , Zhao Shuchun , Kong Christina , Richardson Donna , O'Byrne Ken J. , Giaccia Amato J. , Koong Albert C. 
Published: October 2005

Purpose To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression. Methods We used surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem MS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CD3 (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes. Results SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by MS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CD3 staining (P = .01). Expression of galectin-1 and CD3 were significant predictors for overall survival on multivariate analysis. Conclusion Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege.
Towards an understanding of adsorption behaviour in non-aqueous systems: adsorption of poly(vinyl pyrrolidone) and poly(ethylene glycol) onto silica from 2H, 3H-perfluoropentane
Authors: Paul Alison , Griffiths Peter C , Rogueda Philippe G 
Published: October 2005

Abstract
The adsorption behaviour of low molecular weight poly(ethylene glycol) (PEG 600) and poly(vinyl pyrrolidone) (PVP K25) to silica particles has been investigated at room temperature (21°C) in the partially fluorinated solvent 2H,3H-perfluoropentane (HPFP). PVP (absorbed amount, Γ = 12 mgg−1) was found to adsorb more strongly than PEG (Γ = 4 mgg−1). Both of these values were higher than observed in water. In a further distinction to the aqueous case, where PVP displaces PEG from the interface, no competitive adsorption effects were observed between these two polymers in HPFP, with the adsorbed amounts of each polymer being unchanged by the presence of the other. The stability of silica suspensions in HPFP was primarily dependent on the presence of PVP; PEG/silica systems were unstable, but PVP/silica and PEG/PVP/silica systems formed stable suspensions. All suspensions were destabilized by the addition of small (0.15 wt%) amounts of water. The observations made in this work would point to a flocculation phenomenon due to the addition of water, and not Ostwald ripening. The mechanism of this destabilization is likely to be water acting as a flocculation bridge between particles.
Pharmacokinetic interaction between 5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo (4,3-d) pyrimidine-7-one (DA-8159) and nitroglycerin in rats
Authors: Lee Shin Jung , Bae Soo Kyung , Lee Myung Gull , Kwon Jong Won , You Moohi , Lee Duk Chul 
Published: October 2005

Abstract
The pharmacokinetic interaction between 5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo (4,3-d)pyrimidine-7-one (DA-8159), a new erectogenic, and nitroglycerin has been evaluated in rats. Male Sprague-Dawley rats received DA-8159 (30 mgkg−1) as a single intravenous or oral dose with the simultaneous single intravenous administration of nitroglycerin (2.5 mgkg−1). After simultaneous intravenous administration, the total area under the plasma concentration-time curve from time zero to time infinity (AUCinf) of DA-8159 (746 vs 457 μg min mL−1) was found to be significantly greater than with DA-8159 alone. Also, after simultaneous intravenous administration total body clearance (CL) (40.2 vs 65.6 mL min−1 kg−1), renal clearance (CLR) (1.65 vs 5.11 mL min−1 kg−1), and nonrenal clearance (CLNR) (38.3 vs 60.2 mL min−1 kg−1) of DA-8159 were significantly slower compared with DA-8159 alone. The slower CLNR of DA-8159 could have been due to the inhibition of the metabolism of DA-8159 by nitroglycerin, since DA-8159 is metabolized via CYP3A1/2 in rats and nitroglycerin inhibits CYP3A1/2 in rats. The slower CLR of DA-8159 could have been due to the urine flow rate-dependent CLR of DA-8159 in rats. After the simultaneous intravenous administration of nitroglycerin and DA-8159, the AUCinf of nitroglycerin was significantly smaller (635 vs 960 μg min mL−1), which could have been due to the cardiac output-dependent CL of nitroglycerin. However, after the oral administration of DA-8159, the pharmacokinetic parameters of DA-8159 with and without the intravenous administration of nitroglycerin became comparable. This was not due to the decrease in nitroglycerin's gastrointestinal absorption of DA-8159, but could have been due to changes in nitroglycerin's intestinal first-pass effect of DA-8159. Human studies are required to determine the administration time of DA-8159 when nitroglycerin is concomitantly taken.
The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis
Authors: Don Burl R , Spin Gregory , Rose Aubri , Nestorov Ivan , Hutmacher Matt , Kaysen George A 
Published: October 2005

Abstract
Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-α TNF-α The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-α receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL−1 and C-reactive protein levels &lt;5 mg L−1 (five men, one woman, age range 34–59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13–16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose
Synthesis and pharmacological effects of new, N-substituted soft anticholinergics based on glycopyrrolate
Authors: Ji F , Wu W , Dai X , Mori N , Wu J , Buchwald P , Bodor N 
Published: October 2005

Abstract
To reduce the possibility of systemic side-effects in locally administered anticholinergics, two new N-substituted glycopyrrolate analogues designed using soft drug design approaches have been synthesized and evaluated in vitro and in vivo. Because stereospecificity is known to be important at muscarinic receptors, the new compounds SGM and SGE also have been prepared as their pure 2R isomers, 2R-SGM and 2R-SGE, by starting from optically pure (-)-cyclopentylmandelic acid, and the corresponding isomers were indeed found to be more active. The new soft glycopyrrolates were chemically more stable under acidic conditions, and the ethyl esters SGE were more stable than the methyl esters SGM. The new compounds were also found to be quite susceptible to extrahepatic metabolism, having half-lives of 20–30 min in rat plasma (in vitro), consistent with their soft nature. Binding studies at human muscarinic receptors (M1−M4) and guinea-pig ileum assays found 2R-SGM and 2R-SGE to have potencies somewhat less than, but close to, those of glycopyrrolate and N-methylscopolamine. They caused pupil dilation in rabbit eyes, but their mydriatic effects lasted for considerably less time than that of glycopyrrolate, and they did not induce dilation of the pupil in the contralateral, water-treated eyes, indicating that, in agreement with their soft nature, they are locally active, but safe and with a low potential to cause systemic side-effects.
Role of lupeol and its ester on cyclophosphamide-induced hyperlipidaemic cardiomyopathy in rats
Authors: Sudharsan P T , Mythili Y , Sudhahar V , Varalakshmi P 
Published: October 2005

Abstract
Cyclophosphamide, an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In this study, lupeol, a pentacyclic triterpene isolated from Crataeva nurvala stem bark, and its ester, lupeol linoleate, were investigated for their possible hypocholesterolaemic effects against cyclophosphamide-induced lipidaemic instabilities. Male albino Wistar rats were categorized into 6 groups. Group I served as control. Rats in groups II, V and VI were injected intraperitoneally with a single dose of cyclophosphamide (200 mg kg−1) dissolved in saline. Cyclophosphamide-treated groups V and VI respectively received lupeol and lupeol linoleate (50 mg kg−1), dissolved in olive oil, for 10 days by oral gavage. Groups III and IV served as drug controls and were administered lupeol and lupeol linoleate, respectively. Cyclophosphamide administration induced abnormal changes in serum lipoproteins and lipid fractions in both serum and cardiac tissue. The activity of lipid metabolizing enzymes was distorted significantly in the cyclophosphamide-treated rats. The cyclophosphamide-treated rats also showed extensive intermuscular haemorrhage in histology. Lupeol and its ester reversed the above alterations induced by cyclophosphamide. This study encapsulates the early lipaemic abnormalities in the heart tissue of cyclophosphamide-treated rats. Treatment with lupeol linoleate was more effective than lupeol in rendering protection to the cardiac tissue challenged by cyclophosphamide.
Dietary palm olein oil augments cardiac antioxidant enzymes and protects against isoproterenol-induced myocardial necrosis in rats
Authors: Narang D , Sood S , Thomas M , Maulik S K , Dinda A K 
Published: October 2005

AbstractWistar rats, 150–200g, of either sex, were fed daily with commercial rat diet supplemented with palm olein oil in two doses (5% v/w (n = 16) and 10% v/w (n = 16) of diet) for 30 days. Control rats (n = 16) were fed with normal diet. On the 29th and 30th days, 8 rats from each group were administred isoproterenol (85 mg/kg, s.c., 24-h interval). On the 31st day, all rats were sacrificed and myocardial tissues were studied for thiobarbituric acid reactive substances (TBARS), antioxidant enzymes and light microscopic changes, along with the ferric-reducing ability of plasma (FRAP). A significant rise in myocardial superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity and FRAP level were observed in rats fed with palm olein oil. Isoproterenol caused an increase in myocardial oxidative stress in control rats, as evidenced by an increase in myocardial TBARS level, reduction in FRAP and myocardial SOD, catalase and GPx activity, along with focal necrosis of cardiac muscle fibres on light microscopy. The rise in myocardial TBARS and depletion of SOD and catalase activity following isoproterenol administration were prevented in palm-olein-oil-supplemented diet-fed rats at both doses. Isoproterenol-induced myocardial light-microscopic changes were also prevented in the treated groups. The results suggest that dietary palm olein oil caused augmentation of myocardial antioxidant enzymes and protected against isoproterenol-induced myocardial necrosis and associated oxidative stress.
Distribution of sigma receptors in EMT-6 cells: preliminary biological evaluation of PB167 and potential for in-vivo PET
Authors: Colabufo Nicola Antonio , Berardi Francesco , Contino Marialessandra , Niso Mauro , Perrone Roberto , Tortorella Vincenzo , Fazio Ferruccio , Matarrese Mario , Moresco Rosa Maria 
Published: October 2005

Abstractσ1 and σ2 receptors have been detected in many tissues and are highly expressed in several tumour cell lines from various tissues. The high level of expression observed for σ receptors and their involvement in cell proliferation and apoptosis has led to the development of several σ ligands in order to obtain a molecular probe for in-vivo diagnostic imaging techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT). The EMT-6 cells implanted in mice were a good model for evaluating the proliferation of solid tumours by in-vivo PET. Moreover, we developed the σ ligand PB167, a cyclohexylpiperazine derivative, previously evaluated for σ2 receptor affinity and activity in standard protocols. The related results encouraged us to verify if this compound could be developed as a radiotracer for in-vivo PET in order to visualize σ2 receptors expressed in EMT-6 cells when implanted in mice. This perspective was thought to be favourable because PB167 bears a methoxy substituent on the tetraline nucleus, an easy point for 11C labelling. The aims of this preliminary study were both to assess the relative distribution of σ1 and σ2 receptors in EMT-6 cells and to verify if PB167 could be developed as a σ2 radiotracer for in-vivo PET. The results showed that both σ1 and σ2 receptors were overexpressed in EMT-6 cells and that the ligand PB167 can be positively considered for radiosynthesis preparation in order to suitably visualize σ2 receptors by the in-vivo PET technique and correlate their presence to tumour proliferation.
Dietary fatty acid unsaturation levels, lipoprotein oxidation and circulating chemokine in experimentally induced atherosclerotic rats
Authors: El Seweidy Mohamed M , El-Swefy Sahar E , Abdallah Fatma R , Hashem Reem M 
Published: October 2005

Abstract
The dietary balance of long-chain fatty acids may influence processes involving leukocyte endothelial interactions, such as atherogenesis and inflammation. The relationship between proatherogenic lipoproteins and chemotactic motility is still controversial. However, the interaction of the former can increase recruitment of monocytes to the vessel walls and accelerate the events of atherogenesis. The current study examined the effects of unsaturated fatty acid levels on the oxidative susceptibility of lipoprotein, chemokine expressions and their relationship to atherosclerotic lesion development in experimental rats. Male Wistar rats were fed an atherogenic diet for 4 months and the diet was then supplemented with 10% v/w of virgin olive oil (OO group), sunflower oil (SO group) or fish oil (FO group) for 4 and 8 weeks. Blood samples were collected at four time points: at baseline, after feeding with the atherogenic diet and during the dietary regimen (4 and 8 weeks). Plasma lipid profile and lipoprotein oxidative susceptibility (LOS), C-reactive protein (CRP), monocyte chemoattractant protein (MCP-1), and regulated upon activation normal T-cell expressed and secreted (RANTES) were measured. The superoxide dismutase (SOD) and reduced glutathione (GSH) antioxidant activities were also studied in aortic segments. Histological assessment of the aortic segment was determined. Compared to baseline data, the high-fat and cholesterol-enriched diet increased atheroma formation, plasma LOS and inflammatory indexes (CRP, MCP-1, RANTES). However, it dramatically reduced aortic SOD and GSH contents. Dietary treatment of atherosclerotic rats with OO greatly reduced LOS and remarkably increased aortic SOD and GSH contents as compared to the SO- and FO-treated groups. The FO-supplemented diet had a more pronounced lowering effect on MCP-1 and RANTES compared to the OO and SO diets. In conclusion, this study demonstrated a strong relationship between LOS and circulating levels of chemokines. OO is a potent antioxidant and moderate anti-inflammatory, which effectively reduced aortic atherosclerotic lesions more than the SO- or FO-treated groups in male Wistar rats.
Statin-induced apoptosis linked with membrane farnesylated Ras small G protein depletion, rather than geranylated Rho protein
Authors: Matzno Sumio , Yasuda Shinya , Juman Sachiko , Yamamoto Yukiko , Nagareya-Ishida Noriko , Nakabayashi Toshikatsu , Matsuyama Kenji , Tazuya-Murayama Keiko 
Published: October 2005

Abstract
Rhabdomyolysis is a severe adverse effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). This myopathy is strongly enhanced by the combination with statins and fibrates, another hypolipidaemic agent. We have evaluated the initial step of statin-induced apoptosis by the detection of membrane flip-flop using flow cytometric analysis. L6 rat myoblasts were treated with various statins (atorvastatin (3 μm), cerivastatin (3 μm), fluvastatin (3 μm), pravastatin (3 mm), or simvastatin (3 μm)) for 2, 4 or 6 h followed by reacting with FITC-conjugated annexin V for the detection of initial apoptosis signal (flip-flop). Various statin-treated myoblasts were significantly stained with FITC-annexin V at 6 h, whereas they were not detected at 2 h. Moreover, immunoblot analysis indicated that when the cells were treated with cerivastatin (3 μm), membrane-associated Ras protein was activated and detached until 6 h, resulting in cell death through the consequent activation of caspase-8. On the other hand, since cytosolic Ras activation did not activate, there is still an unknown mechanism in statin-related Ras depletion. In conclusion, statin-induced apoptosis in muscular tissue was directly initiated by the farnesyl-anchored Ras protein depletion from cell membrane with subsequent apoptosis.