bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of Tumor Response and Survival With Erlotinib in Patients With Non—Small-Cell Lung Cancer
Authors: Pérez-Soler Román , Chachoua Abraham , Hammond Lisa A. , Rowinsky Eric K. , Huberman Mark , Karp Daniel , Rigas James , Clark Gary M. , Santabárbara Pedro , Bonomi Philip 
Published: August 2004

Purpose Erlotinib is a highly specific epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. This phase II study of erlotinib in patients with HER1/EGFR-expressing non–small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement. Patients and Methods Fifty-seven patients received an oral, continuous daily dose of 150 mg of erlotinib. Assessments of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, supplemented with a lung cancer module, Quality of Life Questionnaire LC13, was used to measure health-related quality of life. Additional analyses were performed to identify predictors of response and survival. Results The objective response rate was 12.3% (95% CI, 5.1% to 23.7%). Responses were observed regardless of type or number of prior chemotherapy regimens. Median survival time was 8.4 months (95% CI, 4.8 to 13.9 months), and the 1-year survival rate was 40% (95% CI, 28% to 54%). Erlotinib therapy was associated with tumor-related symptom improvement. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in 75% and 56% of patients, respectively. One patient experienced toxicity consisting of severe grade 3 rash and diarrhea. Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model, whereas HER1/EGFR staining intensity was not. Additionally, survival correlated with the occurrence and severity of rash. Conclusion Erlotinib was active and well tolerated in this patient population, and further clinical development is clearly warranted. Cutaneous rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies.
Patient Beliefs and Tamoxifen Discontinuance in Older Women With Estrogen Receptor—Positive Breast Cancer
Authors: Fink Aliza K. , Gurwitz Jerry , Rakowski William , Guadagnoli Edward , Silliman Rebecca A. 
Published: August 2004

Purpose To investigate the patterns and predictors of tamoxifen discontinuance throughout a 2-year period in a cohort of women 65 years or older with newly diagnosed, estrogen receptor (ER)–positive breast cancer, focusing on the role of patients’ beliefs about the risks and benefits of tamoxifen therapy. Subjects and Methods We enrolled a convenience sample of women cared for in four geographic regions of the United States with stage 1 (≥ 1 cm), stage II, or stage IIIA disease; no prior history of breast cancer; and no simultaneously diagnosed second primary breast cancer. Data sources included medical records and telephone interviews with patients at 3, 6, 15, and 27 months following definitive surgery. Results Of the 597 women with ER-positive tumors, 516 women (86%) were prescribed tamoxifen, and of these, 88 (17%) stopped taking tamoxifen during the 2-year follow-up period. Of the women who stopped taking tamoxifen, the majority (68%) took it for less than 1 year. Women with neutral or negative beliefs about the value of tamoxifen (3.0; 95% CI, 1.6 to 5.6) and those with positive nodes (odds ratio = 2.5; 95% CI, 1.0 to 6.3) were more likely to discontinue tamoxifen therapy. Conclusion How women with early-stage breast cancer perceive the risks and benefits of tamoxifen therapy seems critical for sustaining adherence to adjuvant tamoxifen therapy. Interventions designed to educate women about the benefits and risks of tamoxifen therapy may help to reduce discontinuance.
Phase I and Pharmacokinetic Study of the Novel Oral Cell-Cycle Inhibitor Ro 31-7453 in Patients With Advanced Solid Tumors
Authors: Dupont Jakob , Bienvenu Bryan , Aghajanian Carol , Pezzulli Sandra , Sabbatini Paul , Vongphrachanh Phothisath , Chang Christine , Perkell Christina , Ng Kenneth , Passe Sharon , Breimer Lars , Zhi Jianguo , DeMario Mark , Spriggs David , Soignet Steven L. 
Published: August 2004

Purpose To determine maximum tolerated dose, pharmacokinetics (PK), and safety of Ro 31-7453, a novel, oral cell-cycle inhibitor. Patients and Methods Using an accelerated dose-escalation schedule, 48 patients with advanced solid tumors were treated with doses of Ro 31-7453 ranging from 25 to 800 mg/m2/d given for 4 consecutive days, every 3 weeks. The total daily dose was taken as a single dose (schedule A) or divided into two equal doses taken 12 hours apart (schedule B). PK samples of blood and urine were collected on the first and last days of dosing in cycles 1 and 2. Results Forty-five patients completed at least one cycle of therapy. Myelosuppression and stomatitis were dose-limiting toxicities, occurring at the 800 mg/m2/d dose level for both schedules. Toxicity was independent of body-surface area, leading to the recommended phase II flat dose of 1,000 mg daily for 4 days for both schedules. Common adverse events included diarrhea, nausea, vomiting, fatigue, alopecia, and elevated liver-function tests. One death, related to neutropenic sepsis, occurred on study. The PK of the parent compound and major metabolites were apparently linear, with a half-life of approximately 9 hours and a maximum concentration of approximately 4 hours. Minor antitumor activity was observed against carcinoma of the lung, breast, pancreas, and ovary. Conclusion Ro 31-7453 was well tolerated, with manageable adverse effects. Significant PK variability (absorption, metabolism, and excretion) was observed, and a substantial number of additional patients are needed to confirm the recommended phase II dose. Additional pharmacology and phase II studies are under way to explore the dose-toxicity relationship.
The Microanatomic Location of Metastatic Melanoma in Sentinel Lymph Nodes Predicts Nonsentinel Lymph Node Involvement
Authors: Dewar D.J. , Newell B. , Green M.A. , Topping A.P. , Powell B.W.E.M. , Cook M.G. 
Published: August 2004

Purpose Sentinel node biopsy is now widely accepted as the most accurate prognostic indicator in melanoma, and is important in guiding management of patients with clinical stage I or II disease. Patients with a positive sentinel node have conventionally undergone completion lymphadenectomy (CLND) of the involved basin, but only 20% have involvement beyond the sentinel node, suggesting that CLND may be unnecessary for the other 80% of patients. This study seeks to identify criteria that might be used to be more restrictive in selecting those who should undergo CLND. Methods A total of 146 patients were identified who had had a positive sentinel node biopsy for malignant melanoma. Their sentinel nodes and lymphadenectomy specimens were re-evaluated pathologically. The metastatic melanoma in each sentinel node was assessed according to its microanatomic location within the node (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive), and this was correlated with the presence of involved nonsentinel nodes in the CLND. The depth of the metastases from the sentinel node capsule was also recorded. Results The metastatic deposits in the sentinel node were subcapsular in 26.0% of patients. None of these patients had any nonsentinel nodes involved on CLND. In the patients whose sentinel node metastases had a different microanatomic location, the rate of nonsentinel node involvement was 22.2% overall. Conclusion The microanatomic location of metastases within sentinel nodes predicts nonsentinel lymph node involvement. In patients with only subcapsular deposits in the sentinel node, it is possible that CLND could safely be avoided.
Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats
Authors: Filho Ademar A da Silva , Silva Márcio L Andrade e , Carvalho José Carlos T , Bastos Jairo K 
Published: August 2004

Abstract
The bioactivity-guided phytochemical investigation of the crude hydralcoholic extract of Nectandra megapotamica was carried out using the abdominal constriction test in mice, which led to the isolation of three active compounds: α-asarone (1), galgravin (2) and veraguensin (3). The crude extract (EBCA, 300 mg kg−1) and isolated compounds 1, 2, and 3, at different doses, were evaluated using the acetic acid-induced abdominal constriction test in mice, carrageenan-induced paw oedema in rats, and hot plate tests in rats. The EBCA showed a significant effect in the abdominal constriction and hot plate tests, but did not show activity in the rat paw oedema assay. All isolated compounds displayed activity in the abdominal constriction test, but only compound 1 was active in the hot plate test. Compounds 2 and 3 displayed activity in the anti-inflammatory assay. It was suggested that the analgesic effects obtained for EBCA could be due mainly to the presence of its major compound, α-asarone (1).
In-vitro trypanocidal activity evaluation of crude extract and isolated compounds from Baccharis dracunculifolia D. C. (Asteraceae)
Authors: Filho Ademar A da Silva , Bueno Paula C Pires , Gregório Luís E , Silva Márcio L Andrade e , Albuquerque Sérgio , Bastos Jairo K 
Published: August 2004

Abstract
We have performed a trypanocidal bioactivity-guided study of Baccharis dracunculifolia (Asteraceae), the main botanical origin of Brazilian green propolis. The leaf rinse extract of B. dracunculifolia, at a concentration of 3.0 mg mL−1, displayed 100% lysis of trypomastigote forms of the Y strain of Trypanosoma cruzi (2 times 106 parasites mL−1). The chromatographic fractionation of the leaf rinse, using several techniques, afforded the isolation of the compounds isosakuranetin (1), aromadendrin-4′-methylether (2), baccharis oxide (3), ferulic acid (4), dihydrocinnamic acid (5), 3-prenyl-4-(dihydrocinnamoyloxy)-cinnamic acid (6), and friedelanol (7). The chemical structures of all compounds were established by UV-vis, 1H and 13C NMR data analysis in comparison with the literature. Compounds 1 and 3 were the most active in the trypanocidal assay, showing IC50 values (inhibitory concentration required for 50% inhibition) of 247.6 and 249.8 μM, respectively. Compounds 2, 4, and 6 displayed moderate activity, whilst compounds 5 and 7 were inactive.
Improved drug dissolution and product characterization using a crescent-shaped spindle
Authors: Qureshi Saeed A 
Published: August 2004

Abstract
Drug release characteristics of two amoxicillin capsule products, 250 and 500 mg strength each, have been described using USP Paddle and crescent-shaped spindles. Using the same spindles, dissolution experiments were conducted with USP disintegrating (prednisone) and non-disintegrating (salicylic acid) calibrator tablets. Dissolution tests were conducted at 50 and 25 rev min−1 using USP Paddle and crescent-shaped spindles, respectively. In all cases, even with the higher 50 rev min−1, lower percent drug release results were observed with the Paddle spindle than with the crescent-shaped spindle, which was operated at 25 rev min−1. The observed lower dissolution for amoxicillin capsule products (&lt; 36 vs &gt; 87% at 30 min) and USP prednisone calibrator tablets (45.5 vs 99.8% at 30 min) with Paddle spindles appeared to occur because of the accumulation of the disintegrated material (cone formation) at the bottom, thus restricting product-medium interaction. Crescent-shaped spindles did not allow any accumulation of the product and provided improved interaction by mixing and stirring, and thus appeared to provide true drug dissolution characteristics of the products. On the other hand, in the case of non-disintegrating USP salicylic acid tablets (18.5 vs 24.4% at 30 min), lower results with Paddle spindles appeared to be because of stagnation of the tablets, which provided poor product-medium interaction for the surface touching the vessel surface. In this case, the crescent-shaped spindles moved the tablets at the base of the vessel, providing improved and efficient product-medium interaction, thus appearing to reflect truer dissolution characteristics of the tablets. The results highlight the possible artifacts of the USP Paddle spindle, which could lead to inaccurate characterization of drug release properties of test products. As reported previously, the artifacts of high variability in results and lack of relevance to product properties appeared to be related to poor mixing and variable hydrodynamics within a dissolution vessel. Results from this study provide further evidence that these artifacts might be addressed adequately using the crescent-shaped spindle, thus resulting in improved drug release as well as better product characterization.
Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunum
Authors: Sandri Giuseppina , Rossi Silvia , Ferrari Franca , Bonferoni Maria Cristina , Zerrouk Naima , Caramella Carla 
Published: August 2004

Abstract
The influence of the molecular weight on mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid (1878, 693 and 202 kDa) has been evaluated. The mucoadhesive properties were investigated using buccal and vaginal porcine mucosa by means of a tensile stress method and using rat jejunum by means of an inclined plane method. The mucoadhesive performances observed using animal tissues were compared with the mucoadhesive properties observed using submaxillary or gastric mucin dispersions. The penetration enhancement properties were investigated using porcine buccal epithelium membrane or vaginal tissue and a cell monolayer (Caco-2 cell line). Chitosan hydrochloride, already described as a penetration enhancer towards buccal and vaginal mucosae and Caco-2 cell monolayers, was used as reference. Aciclovir (acyclovir), a poorly soluble and absorbable drug, commonly used in the treatment of Herpes simplex virus (type I and II), was used as the model drug. Unlike chitosan hydrochloride, which does not show any mucoadhesive potential at pH close to neutrality (buccal and intestinal), all hyaluronic acid grades show mucoadhesive properties in all the environments considered (buccal, vaginal and intestinal). In all cases, a decrease in molecular weight of hyaluronic acid produced an increase in the mucoadhesive performance. The hyaluronic acid with the lowest molecular weight (202 kD) exhibited the best penetration enhancement properties, that, depending on the substrate under consideration, was either comparable with or even better than chitosan hydrochloride. Therefore, this grade would be the most promising for buccal, vaginal and intestinal delivery of aciclovir.
The in-vivo effect of bakumondo-to (TJ-29), a traditional Japanese medicine used for treatment of chronic airway disease, on cytochrome P450 1A2, xanthine oxidase and N-acetyltransferase 2 activity in man
Authors: Saruwatari Junji , Hisaeda Shinichirou , Higa Yoko , Tomiyasu Yuko , Nakagawa Kazuko , Ishizaki Takashi 
Published: August 2004

Abstract
In Japan, patients with chronic airway disease are administered bakumondo-to (TJ-29), a mixture of six herbal components. We have assessed the effects of TJ-29 on the activities of cytochrome P450 (CYP) 1A2, xanthine oxidase and N-acetyltransferase 2 in 26 healthy subjects under a double-blind, randomized, placebo-controlled cross-over study design. The baseline activities of the three enzymes were assessed by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine. Thereafter, the subjects received a thrice-daily 3.0-g dose of TJ-29 or placebo for seven days, and underwent the same caffeine test on the post-dose days 1 and 7. No statistically significant difference was observed in the activity of the three enzymes between those at baseline, and on day 1 after dosing with TJ-29 or placebo. The mean activity of CYP1A2, xanthine oxidase and N-acetyltransferase 2 tended to be lower on day 7 after dosing with TJ-29 compared with those at baseline and on day 7 after dosing with placebo. However, these changes were not statistically significant in CYP1A2 (P=0.120), xanthine oxidase (P=0.123) or N-acetyltransferase 2 (P=0.056). In conclusion, TJ-29 did not appear to substantially affect the activity of CYP1A2, xanthine oxidase or N-acetyltransferase 2 in man.
Phytochemical analysis and anti-allergic study of Agave intermixta Trel. and Cissus sicyoides L.
Authors: Quílez A M , Saenz M T , García M D , de la Puerta R 
Published: August 2004

Abstract
Agave intermixta Trel. (Maguey) and Cissus sicyoides L. (Bejuco caro) are Caribbean plant species from the Dominican Republic used locally in traditional popular medicine that have shown an anti-inflammatory effect in experimental animal models. A phytochemical analysis on these species allowed us the isolation and identification of the steroidal sapogenins hecogenin and diosgenin from Maguey and the hydroxystilbene resveratrol from Bejuco caro. The effects of these plant extracts and their isolated constituents on compound-48/80-induced histamine release from peritoneal mast cells were investigated. Significant inhibition was produced by 0.5 mg mL−1 of a methanolic extract of Bejuco (41.1%) and by its constituent resveratrol (82.4%) at a dose of 250 μM. However, none of the steroidal sapogenins from A. intermixta showed a significant inhibitory effect on histamine release from mast cells. From these results, it can be deduced that the in-vitro anti-allergic activity towards the release of histamine from mast cells shown by the methanolic extract of C. sicyoides may be mediated by its constituent resveratrol and might contribute to the anti-inflammatory activity shown by this species.
Effect of dexamethasone, 2-bromopalmitate and clofibrate on L-FABP mediated hepatoma proliferation
Authors: Rajaraman G , Burczynski F J 
Published: August 2004

Abstract
Cytosolic liver fatty acid binding protein (L-FABP) is involved in many intracellular functions including cellular mitogenesis. We investigated the role of L-FABP and the plasma membrane liver fatty acid binding proteins (L-FABPpm) in the modulation of hepatoma growth and proliferation, hypothesizing that agents that affect either the content of, or ligand binding to, L-FABP would affect hepatocellular mitogenesis. L-FABP expressing 1548-rat hepatoma cells were treated with 0.5 μM dexamethasone or 500 μM clofibrate for 4 days to downregulate and upregulate L-FABP expression, respectively. The competitive inhibitor 2-bromopalmitate (BrPA, 600 μM) was used to inhibit ligand binding to L-FABP. The peripherally present plasma membrane fatty acid transporter was inactivated by treating cells with 1:50 rabbit antisera (FABP-Ab) raised against L-FABP. Western blot analysis was used to monitor L-FABP levels while [3H]-thymidine incorporation and growth curves were used to monitor hepatocellular proliferation. [3H]-Palmitate clearance studies were performed using monolayer cultures. Palmitate clearance in dexamethasone-, BrPA- and FABP-Ab-treated cells was significantly reduced when compared with control (P &lt; 0.05), while clofibrate treatment moderately increased the rate. [3H]-Thymidine incorporation by dexamethasone- and BrPA-treated cells was significantly lower than control (P &lt; 0.05), suggesting that hepatocellular proliferation was inhibited. Clofibrate treatment did not statistically affect growth rate. Lowering L-FABP using dexamethasone or interfering with its activity using BrPA significantly affected hepatocellular proliferation. This may be due to the non-availability of long-chain fatty acids or other intracellular mediators that are transported by L-FABP to the nucleus.
An investigation into the biological activity of the selected histidine-containing diketopiperazines cyclo(His-Phe) and cyclo(His-Tyr)
Authors: McCleland K , Milne P J , Lucieto F R , Frost C , Brauns S C , Van De Venter M , Du Plessis J , Dyason K 
Published: August 2004

Abstract
Although cyclic diketopiperazines have been known since the beginning of the century, only now have they attracted considerable interest with respect to their biological activity. The aim of this study was to determine if the diketopiperazines cyclo(L-histidyl-L-phenylalanyl) (cyclo(His-Phe)) and cyclo(L-histidyl-L-tyrosyl) (cyclo(His-Tyr)) have significant biological activity relevant to the treatment of cardiovascular-related disease states, cancer and infectious diseases. Haematological studies were performed, including thrombin substrate binding, blood clotting time, platelet adhesion, platelet aggregation and fibrinolysis assays. A cytotoxicity screening utilizing a tetrazolium-based assay on the cell lines HeLa, WHCO3, and MCF-7 was performed. The whole-cell patch-clamp technique was used to investigate ion-channel activity in ventricular myocytes of rats, and isolated rat heart studies were performed to investigate the cardiac effects involving heart rate and coronary flow rate. Cyclo(His-Tyr) produced a significant prolongation of blood clotting time, slowing of clot lysis and inhibition of ADP-induced platelet adhesion and aggregation (P &lt; 0.05). Cyclo(His-Phe) showed significant (P &lt; 0.05) anti-tumour activity, causing greatest reduction of cell viability in cervical carcinoma cells. Preliminary results from patch-clamp studies indicate that both diketopiperazines caused blocking of sodium and calcium ion channels, but opening of inward rectifying potassium ion channels. In the rat isolated heart studies, cyclo(His-Phe) caused a gradual reduction in heart rate (P = 0.0027) and a decrease in coronary flow rate (P = 0.0017). Cyclo(His-Tyr) significantly increased the heart rate (P = 0.0016) but did not cause any significant change of coronary flow rate (P &gt; 0.05). Cyclo(His-Tyr) showed notable (P &lt; 0.05) antibacterial activity and both diketopiperazines showed excellent antifungal activity (P &lt; 0.05). These observations reveal diketopiperazines to be ideal lead compounds for the rational design of an agent capable of preventing metastasis, inhibiting tumour growth, and as potential chemotherapeutic, antiarrhythmic and antihypertensive agents, as well as potential antibacterial and antifungal agents.