bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Pemetrexed Plus Carboplatin in Malignant Pleural Mesothelioma
Authors: Ceresoli Giovanni L. , Zucali Paolo A. , Favaretto Adolfo G. , Grossi Francesco , Bidoli Paolo , Del Conte Guido , Ceribelli Anna , Bearz Alessandra , Morenghi Emanuela , Cavina Raffaele , Marangolo Maurizio , Parra Hector J. Soto , Santoro Armando 
Published: March 2006

PurposeThis multicenter, phase II clinical study was conducted to evaluate the activity of the combination of pemetrexed and carboplatin in patients with malignant pleural mesothelioma (MPM).Patients and MethodsChemotherapy-naive patients with measurable disease and adequate organ function, who were not eligible for curative surgery, received pemetrexed 500 mg/m2and carboplatin area under the plasma concentration-time curve of 5 mg/mL/min, administered intravenously every 21 days. All patients received folic acid and vitamin B12supplementation. Pemetrexed was provided within the Expanded Access Program.ResultsA total of 102 patients were enrolled. An objective response was achieved in 19 patients (two complete and 17 partial responses), for a response rate of 18.6% (95% CI, 11.6% to 27.5%). Forty-eight patients (47.0%; 95% CI, 37.1% to 57.2%) had stable disease after treatment. Overall, 67 patients (65.7%) achieved disease control (95% CI, 55.6% to 74.8%). Median time to progression was 6.5 months; median overall survival time was 12.7 months. Compliance to treatment was excellent, with a relative dose-intensity of 97% for pemetrexed and 98% for carboplatin. Toxicity was mild, with grade 3 or 4 neutropenia occurring in 9.7% of total cycles and grade 3 or 4 anemia occurring in 3.5% of total cycles. Nonhematologic toxicity was negligible.ConclusionTreatment with pemetrexed and carboplatin was active and well tolerated in patients with MPM. Disease control rate, time to disease progression, and overall survival were similar to the results achieved with the standard regimen of pemetrexed and cisplatin, suggesting that the carboplatin combination could be an alternative option for these patients.
Phase III Study of Gemcitabine and Cisplatin With or Without Aprinocarsen, a Protein Kinase C-Alpha Antisense Oligonucleotide, in Patients With Advanced-Stage Non–Small-Cell Lung Cancer
Authors: Paz-Ares Luis , Douillard Jean-Yves , Koralewski Piotr , Manegold Christian , Smit Egbert F. , Reyes José Miguel , Chang Gee-Chen , John William J. , Peterson Patrick M. , Obasaju Coleman K. , Lahn Michael , Gandara David R. 
Published: March 2006

Purpose To determine whether aprinocarsen, an antisense oligonucleotide directed against protein kinase C-alpha, when added to the chemotherapy regimen of gemcitabine and cisplatin improved survival in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with previously untreated stage IIIB/IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned to either a control arm of gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1, or experimental arms consisting of the identical chemotherapy plus aprinocarsen 2 mg/kg/d as continuous infusion for 14 days, starting on either day 1 or 3 days before chemotherapy. Cycles were repeated every 21 days. Results A total of 670 patients were randomly assigned between the control (n = 328) and experimental arms (n = 342). Due to the results from another phase III study of aprinocarsen in NSCLC, further enrollment was stopped, and the study was terminated early. The median number of cycles was four on the control arm and three on the combined experimental arms. Median overall survival was not different between the two groups (control, 10.4 months [95% CI, 8.6 to 12.2]; experimental, 10.0 months [95% CI, 8.4 to 10.8]; P = .613; hazard ratio = 1.05 [95% CI, 0.88 to 1.25]). Response rates (control arm, 35.0%; experimental arms, 28.9%; P = .124) and other time-to-event measures were not significantly different. Grade 3 and 4 toxicities were significantly increased for thrombocytopenia (P < .0001), epistaxis, and thrombosis/embolism in the experimental arms. Conclusion Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.
Missed Opportunities: Racial Disparities in Adjuvant Breast Cancer Treatment
Authors: Bickell Nina A. , Wang Jason J. , Oluwole Soji , Schrag Deborah , Godfrey Henry , Hiotis Karen , Mendez Jane , Guth Amber A. 
Published: March 2006

Purpose Underuse of adjuvant therapy is a potentially important and remediable explanation for the inferior survival of minority women with breast cancer. We sought to measure a racial disparity in the underuse of adjuvant treatments for early-stage breast cancer and to identify associated factors. Methods Cross-sectional study with review of all inpatient and outpatient medical records of 677 women treated surgically for a primary American Joint Committee on Cancer stage I or II breast cancer in 1999 to 2000. Underuse was defined as omissions of radiation therapy after breast-conserving surgery, adjuvant chemotherapy after resection of hormone-receptor-negative tumors ≥ 1 cm, or hormonal therapy for receptor-positive tumors ≥ 1 cm. Results One hundred forty-five (21%) of 677 women experienced underuse of appropriate adjuvant therapy: 16% in whites, 34% in blacks, and 23% in Hispanics (P < .001). Women referred to medical oncologists were less likely to experience underuse of necessary adjuvant treatments (relative risk [RR] for underuse = 0.2; 95% CI, 0.1 to 0.3). Women who were minorities (RR = 2.0; 95% CI, 1.3 to 3.1), had higher levels of comorbidity (RR = 1.4; 95% CI, 1.1 to 1.8) and lacked insurance (RR = 1.9; 95% CI, 0.9 to 4.0) were at greater risk for underuse. Conclusion Minority women with early-stage breast cancer have double the risk of white women for failing to receive necessary adjuvant treatments despite rates of oncologic consultation similar to those for white women. Oncology referrals are necessary to reduce treatment disparities but are not sufficient to ensure patients' receipt of efficacious adjuvant treatment.
Postradiotherapy Neck Dissection for Lymph Node–Positive Head and Neck Cancer: The Use of Computed Tomography to Manage the Neck
Authors: Liauw Stanley L. , Mancuso Anthony A. , Amdur Robert J. , Morris Christopher G. , Villaret Douglas B. , Werning John W. , Mendenhall William M. 
Published: March 2006

Purpose To determine how to use node response on computed tomography (CT) to indicate the need for neck dissection. Patients and Methods Five hundred fifty patients with lymph node–positive head and neck cancer were treated between 1990 and 2002 with radiotherapy (RT) at a median dose of 74.4 Gy; 24% of these patients (n = 133) were treated with chemotherapy. Three hundred forty-one patients (62%) underwent planned post-RT neck dissection. Physical examination and contrast-enhanced CT were performed 30 days after completion of RT. CT images were reviewed in 211 patients for lymph node size (largest axial dimension) and presence of a focal abnormality (lucency, enhancement, or calcification). By correlating post-RT CT to neck dissection pathology, criteria associated with a low likelihood of residual disease were identified. A subset of patients who fit these criteria of radiographic response who did not undergo post-RT neck dissection was observed for recurrence. Results Radiographic complete response (rCR) was defined as the absence of any large (> 1.5 cm) or focally abnormal lymph node. Correlation of response with neck dissection pathology indicated a negative predictive value of 77% for complete clinical response and 94% for rCR. In 32 patients (median follow-up time, 3.2 years) with rCR who did not undergo post-RT neck dissection, the 5-year ultimate neck control rate (100%) and cause-specific survival rate (72%) were not significantly different from the rates of patients with a negative post-RT neck dissection. Conclusion Patients with rCR 4 weeks after RT can be spared from a post-RT neck dissection regardless of initial node stage.
Can drug-bearing liposomes penetrate intact skin?
Authors: El Maghraby Gamal M M , Williams Adrian C , Barry Brian W 
Published: March 2006

Abstract
Using liposomes to deliver drugs to and through human skin is controversial, as their function varies with type and composition. Thus they may act as drug carriers controlling release of the medicinal agent. Alternatively, they may provide a localized depot in the skin so minimizing systemic effects or can be used for targeting delivery to skin appendages (hair follicles and sweat glands). Liposomes may also enhance transdermal drug delivery, increasing systemic drug concentrations. With such a multiplicity of functions, it is not surprising that mechanisms of liposomal delivery of therapeutic agents to and through the skin are unclear. Accordingly, this article provides an overview of the modes and mechanisms of action of different vesicles as drug delivery vectors in human skin. Our conclusion is that vesicles, depending on the composition and method of preparation, can vary with respect to size, lamellarity, charge, membrane fluidity or elasticity and drug entrapment. This variability allows for multiple functions ranging from local to transdermal effects. Application to dissimilar skins (animal or human) via diverse protocols may reveal different mechanisms of action with possible vesicle skin penetration reaching different depths, from surface assimilation to (rarely) the viable tissue and subsequent systemic absorption.
Significant and prolonged antisense effect of a multifunctional envelope-type nano device encapsulating antisense oligodeoxynucleotide
Authors: Nakamura Yoshio , Yamada Yuma , Kogure Kentaro , Harashima Hideyoshi , Futaki Shiroh 
Published: March 2006

Abstract
A multifunctional envelope-type nano device (MEND) was developed for use as an efficient non-viral system for the delivery of plasmid DNA (pDNA) using octaarginine (R8) as an internalizing ligand. Three types of R8-MENDs were prepared, co-encapsulating luciferase-encoding pDNA and antiluciferase oligodeoxynucleotide (ODN) condensed by three polycations, stearyl octaarginine (STR-R8), poly-l-lysine (PLL) and protamine, and the antisense effects of the ODN-encapsulated R8-MENDs (ODN-MEND) were analysed in-vitro. The ODN-MEND packaged using protamine as a condenser showed a 90% antisense effect 16 h after the transfection, and a persistent antisense effect of over 75% for up to 48 h, which was much more effective than that of LipofectAmine2000. On the other hand, the ODN-MENDs prepared using PLL and STR-R8 as condensers did not show any significant inhibition of luciferase activity. Although there was no specific relation between the physicochemical characteristics of the ODN-MENDs and their antisense effect, the pattern of the antisense effect among the ODN-MENDs was similar to that of the silencing effect of R8-MEND encapsulating plasmid DNA encoding siRNA. These results suggest that R8-MENDs are able to deliver encapsulated DNA to the cytosol as well as to the nucleus, and that protamine can also function as an efficient decondenser, not only in the nucleus but also in the cytosol. In conclusion, we successfully developed an ODN-MEND with a high antisense effect using protamine as a DNA condensing as well as a decondensing agent.
Evaluation of the immune response induced by a nasal anthrax vaccine based on the protective antigen protein in anaesthetized and non-anaesthetized mice
Authors: Sloat Brian R , Cui Zhengrong 
Published: March 2006

Abstract
To better protect against inhalational anthrax infection, a nasal anthrax vaccine based on the protective antigen (PA) protein of Bacillus anthracis could be an attractive alternative to the current Anthrax-Vaccine-Adsorbed (AVA), which was licensed for cutaneous anthrax prevention. Previously, we have demonstrated that an anti-PA immune response comparable with that in mice subcutaneously immunized with PA protein adjuvanted with aluminium hydroxide was induced in both the systemic compartment and the mucosal secretions of the nose and lung of anaesthetized mice when they were nasally immunized with PA protein incorporated into previously reported LPD (Liposome—Protamine—DNA) particles. In this study, we evaluated the anti-PA immune response induced by the nasal PA/LPD particles in non-anaesthetized mice and compared it with that in anaesthetized mice. Our data showed that the anti-PA antibody response and the anthrax lethal toxin-neutralization activity induced by the nasal PA/LPD in non-anaesthetized mice was relatively weaker than that in anaesthetized mice. However, the splenocytes isolated from the nasally immunized mice, anaesthetized and non-anaesthetized, proliferated comparably after in-vitro re-stimulation. By evaluating the uptake of fluorescence-labelled LPD particles by phagocytes in the nasal and broncho-alveolar lavages of mice after the nasal administration, we concluded that the relatively weaker anti-PA immune response in the non-anaesthetized mice might be partially attributed to the reduced retention of the PA/LPD particles in the nasal cavity of the non-anaesthetized mice. Data collected in this study are expected to be useful for future anthrax nasal vaccine studies when mice are used as a model.
Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous ipriflavone in rats
Authors: Chung Hye J , Choi Young H , Lee Myung G , Kim So H 
Published: March 2006

AbstractIn order to find out what types of the hepatic microsomal cytochrome P450 (CYP) isozymes are involved in the metabolism of ipriflavone, ipriflavone at a dose of 20 mg kg−1 (or 15 mg kg−1) was infused in male Sprague—Dawley rats. In rats pretreated with SKF 525-A (a non-specific CYP isozyme inhibitor in rats), the total body clearance (CL) of ipriflavone was significantly slower (29.9% decrease) than that in control rats. This indicates that ipriflavone is metabolized via CYP isozymes in rats, hence various enzyme inducers and inhibitors were used in in-vitro or in-vivo studies in rats. In rats pretreated with 3-methylcholanthrene and phenobarbital (main inducers of CYP1A1/2 and 2B1/2 in rats, respectively), the CL values were significantly higher (153 and 67.2% increases, respectively). In rats pretreated with sulfaphenazole (a main inhibitor of CYP2C11 in rats), the CL was significantly slower (22.5% decrease) than that in control rats. On addition of furafylline (a main inhibitor of CYP1A2 in rats), the in-vitro intrinsic clearance for the disappearance of ipriflavone was significantly slower (50.8% decrease) than that without furafylline. However, the CL values were not significantly different in rats pretreated with orphenadrine and isoniazid (a main inducer of CYP2E1 in rats), and quinine and troleandomycin (main inhibitors of CYP2D1 and 3A23/2 in rats, respectively) compared to controls. These data suggest that ipriflavone could be metabolized mainly via CYP1A1/2, 2B1/2 and 2C11 in rats.
Ethinylestradiol-loaded ultraflexible liposomes: pharmacokinetics and pharmacodynamics
Authors: Garg Minakshi , Mishra Dinesh , Agashe Hrushikesh , Jain Narendra Kumar 
Published: March 2006

Abstract
This study aimed to develop ultraflexible liposomes as an alternative to the oral route, which would enhance the bioavailability and reduce the toxicity of ethinylestradiol. Ultraflexible liposomes of ethinylestradiol using an optimized concentration of surfactants were prepared and characterized in vitro. The effect of surfactant type under non-occlusive conditions on transdermal permeability was assessed. A histopathological study was performed to assess the action of ethinylestradiol on the uterus and ovaries. The pharmacokinetics of free ethinylestradiol (following single oral administration and one day of application to the skin), ultraflexible liposomal ethinylestradiol and non-flexible liposomal ethinylestradiol were studied in female Sprague—Dawley rats. Insignificant differences in size between the ultraflexible liposomal formulations containing optimized concentrations of different surfactants were observed. Ultraflexible liposomes can penetrate through pores much smaller than their own diameter. The transdermal permeability of lipophilic surfactant was greater than that of hydrophilic surfactant. The release of ethinylestradiol from the proposed formulation through rat skin was found to be constant. The histopathological study showed that the ultraflexible liposomal transdermal drug delivery system for ethinylestradiol provided effective contraception by follicular cell lysis, depletion of zona granulosa and ova, and by increasing the uterine mucosal and endometrial proliferation. Encapsulation of ethinylestradiol in ultraflexible liposomes modified the pharmacodynamics and pharmacokinetics of the contraceptive agent, resulting in a marked improvement in bioavailability and optimized therapy.
ATP participates in the regulation of microvessel permeability
Authors: Tanaka Naoko , Nejime Namie , Kagota Satomi , Kubota Yoko , Yudo Keiko , Nakamura Kazuki , Kunitomo Masaru , Shinozuka Kazumasa , Takahashi Koichi , Hashimoto Michio 
Published: March 2006

AbstractWe demonstrated previously that stimulation of the P2Y receptor enhanced the macromolecular permeability of cultured endothelial cell monolayers via the paracellular pathway. To determine whether the P2Y receptor participates in the regulation of permeability in intact microvessels, we have examined the effects of exogenous and endogenous ATP on the permeation of the surface tissue of perfused rat tail caudal artery using a fluorescein isothiocyanate-dextran (FD-4; MW 4400; 1.0 mg mL−1). The permeation of FD-4 was assessed by a confocal fluorescence imaging system. We found that 2-methylthioadenosine 5′-triphosphate, a P2Y receptor agonist, enhanced the fluorescence intensity of FD-4 in the surface of the rat caudal artery tissue and that it was inhibited by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid, a P2 receptor antagonist. Also, noradrenaline, a sympathetic neurotransmitter, and bradykinin, an inflammatory autacoid, enhanced the fluorescence intensity of FD-4 in the surface tissue of the rat caudal artery. The enhancement by noradrenaline was significantly inhibited by the P2 receptor antagonist. In addition, noradrenaline and bradykinin caused the release of ATP, ADP, AMP and adenosine from the endothelium of the rat caudal artery. These results indicated that the exogenous and endogenous ATP increased the macromolecular permeability of blood capillaries via the P2Y receptor. Such purinergic regulation of endothelial permeability may function in physiological and pathophysiological conditions.
Induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea
Authors: Ayoub Shereen , Melzig Matthias F 
Published: March 2006

Abstract
Deposition of amyloid β-peptide as senile plaques in the brain is one of the neuropathological hallmarks of Alzheimer's disease, which is the most prevalent progressive neurodegenerative disease leading to dementia. Neutral endopeptidase is one of the major β-amyloid-degrading enzymes in the brain. To examine the influence of different polyphenols and other natural products from green tea extract (from Camellia sinensis, Theaceae), we used the neuroblastoma cell line SK-N-SH and studied the changes in the specific cellular neutral endopeptidase activity after long-term treatment with these substances. We have shown that caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. We have also shown that the combination of epicatechin, epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induced cellular neutral endopeptidase activity. It is suggested that the enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate.
Rubiae Radix suppresses the activation of mast cells through the inhibition of Syk kinase for anti-allergic activity
Authors: Lee Jun Ho , Kim Nam Wook , Her Erk , Kim Bo Kyung , Choi Wahn Soo , Hwang Keum Hee , Choi Dong Kug , Lim Beong Ou , Han Jeung Whan , Kim Young Mi 
Published: March 2006

Abstract
The effect of extracts from various Oriental medicinal herbs on mast-cell-mediated allergic reactions was investigated in this study. Of these extracts, the medicinal herb Rubiae Radix exhibited the most potent activity in the cells, with an IC50 value (concentration necessary to obtain 50% inhibition of the response) of approximately 35±2.1 μg mL−1, and its inhibition of compound-48/80-induced systemic anaphylaxis by 48.6±8.5% at 300 mg kg−1 in mice. It also inhibited the expression of the pro-inflammatory mediator tumour necrosis factor-α (TNF-α). As for its mechanism of action, Rubiae Radix suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signalling processes, and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. These results suggest that Rubiae Radix suppresses the activation of mast cells through the inhibition of Syk for antiallergic activity.
Withania somnifera improves bone calcification in calcium-deficient ovariectomized rats
Authors: Nagareddy Prabhakara Reddy , Lakshmana M 
Published: March 2006

Abstract
Osteoporosis, characterized by reduction in bone density, is a significant source of mortality among the elderly, particularly in oestrogen-deficient women. We studied the effect of Withania somnifera (WS) root extract (ethanolic), which contains oestrogen-like withanolides for anti-osteoporotic activity. Female Sprague-Dawley rats were either sham operated (n = 12) or ovariectomized (n = 12) and treated with WS/vehicle (65 mg kg−1), orally for 16 weeks (n = 12). All rats were allowed free access to a calcium-deficient diet (0.04% Ca) and distilled water. At termination, urinary excretion of calcium (Ca) and phosphorus (P) and serum levels of Ca, P and alkaline phosphatase (ALP) were measured. Femur and tibia bones were processed for histological (histology), morphological (scanning electron microscopy, SEM), biomechanical strength (impact test) and mineral composition (ash) analysis. Ovariectomized (OVX) rats showed a significant increase in serum ALP levels and urinary Ca and P excretion. Histological findings revealed narrowed, and disappearance of, trabeculae with widened medullary spaces in the OVX group. Ash analysis showed a reduction in ash weight, percent ash, ash Ca, ash P and ash magnesium levels in the OVX group. Further, SEM examination revealed metaphyseal bone loss in femurs and impact test showed a reduction in biomechanical strength of tibias in OVX rats. WS treatment markedly prevented the above changes in OVX rats and thus may be a potential agent in the treatment of osteoporosis.