bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative Twice-Weekly Paclitaxel With Concurrent Radiation Therapy Followed by Surgery and Postoperative Doxorubicin-Based Chemotherapy in Locally Advanced Breast Cancer: A Phase I/II Trial
Authors: Formenti Silvia C. , Volm Matthew , Skinner Kristin A. , Spicer Darcy , Cohen Deidre , Perez Edith , Bettini Anna C. , Groshen Susan , Gee Conway , Florentine Barbara , Press Michael , Danenberg Peter , Muggia Franco 
Published: February 2003

Purpose: Preoperative chemotherapy is the conventional primary treatment in locally advanced breast cancer (LABC). We investigated the safety and efficacy of primary twice-weekly paclitaxel and concurrent radiation (RT) before modified radical mastectomy followed by adjuvant doxorubicin-based chemotherapy. Patients and Methods: Stage IIB (T3N0) to III LABC patients were eligible. Primary chemoradiation consisted of paclitaxel, 30 mg/m2 delivered intravenously for 1 hour twice weekly for a total of 8 to 10 weeks, and concurrent RT (45 Gy at 1.8 Gy/fraction). Modified radical mastectomy was performed at least 2 weeks after completion of chemoradiation or on recovery of skin toxicity. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan. Results: Forty-four patients were accrued. Toxicity from paclitaxel/RT included grade 3 skin desquamation (7%), hypersensitivity (2%), and stomatitis (2%). Postsurgery complications occurred in six patients (14%). The only grade 4 toxicity of postmastectomy chemotherapy was hematologic (10%). Grade 3 toxicities were leukopenia (24%), infection (22%), peripheral neuropathy (17%), arthralgia and pain (17%), stomatitis (12%), fatigue (10%), esophagitis (5%), and nausea (2%). Overall clinical response rate to preoperative paclitaxel and RT was 91%. Thirty-four percent of patients achieved a pathologic response in the mastectomy specimen: 16% pathologic complete responses (clearance of invasive cancer in the breast and axillary contents) and 18% pathologic partial responses (< 10 residual microscopic foci of invasive breast cancer). Conclusion: Twice-weekly paclitaxel with concurrent RT is a feasible and effective primary treatment for LABC. Future studies should compare primary chemoradiation to chemotherapy in LABC.
Thymidylate Synthase Protein Expression in Primary Colorectal Cancer: Lack of Correlation With Outcome and Response to Fluorouracil in Metastatic Disease Sites
Authors: Johnston Patrick G. , Benson Al B. , Catalano Paul , Rao M. Sambasiva , O’Dwyer Peter J. , Allegra Carmen J. 
Published: February 2003

Purpose: The aim of this study was to investigate the utility of quantitating thymidylate synthase (TS) in the primary tumor as a surrogate for metastatic disease sites to predict the likelihood of response and outcome to fluorouracil (FU) treatment in patients with metastatic colorectal cancer. Methods: TS protein expression was evaluated using the TS 106 antibody and the avidin biotin labeling immunohistochemical technique in primary tumor samples from 219 patients with metastatic colorectal cancer. The patients were a representative sample of those patients enrolled into the Eastern Cooperative Oncology Group E2290 protocol that evaluated five separate FU-containing regimens in patients with metastatic residual or recurrent colorectal carcinoma. Results: Our retrospective analysis found that the level and extent of TS protein expression in the primary tumor did not correlate with overall survival in patients with metastatic or recurrent colorectal cancer. A trend toward a direct correlation between the level of TS protein expression and response was noted in tumors that expressed high TS levels. This response advantage for patients expressing high TS levels in the primary tumor was apparent regardless of what FU-based treatment the patient received but was most apparent in the subgroup treated with leucovorin, in which the level of TS expression and response to FU and leucovorin reached statistical significance (P = .034). No significant interaction could be detected between the addition of leucovorin to FU and the level of TS expression in the primary tumor. Conclusion: This study demonstrated that measurement of TS protein levels in the primary tumor tissue does not aid in predicting outcome or response to FU in a metastatic disease site. These assays must be performed on biopsy tissue from the metastatic disease site that is used to radiologically assess response and outcome to treatment.
American Oncologists’ Views of Internet Use by Cancer Patients: A Mail Survey of American Society of Clinical Oncology Members
Authors: Helft Paul R. , Hlubocky Fay , Daugherty Christopher K. 
Published: February 2003

Purpose: Americans are turning more and more frequently to the Internet to obtain health information. The specific effects on patients, doctors, and the clinical encounter are not well known. Methods: A brief mail survey was sent to a systematic sample of 5% of medical oncologists and hematologist/oncologists listed in the membership directory of the American Society of Clinical Oncology. Results: Response rate to this mail survey was 46.2%. Oncologists’ median estimate of the proportion of their patients using the Internet to obtain cancer information was 30%. Subjects responded that, on average, 10 minutes were added to each patient encounter in which Internet information was discussed. Responding oncologists reported that use of the Internet had the ability to simultaneously make patients more hopeful, confused, anxious, and knowledgeable. Forty-four percent of responding oncologists reported that they sometimes or rarely had difficulty discussing Internet information, and only 9% of subjects reported that they sometimes or always felt threatened when patients brought Internet information to discuss. In narrative responses, oncologists reported both positive and negative effects of Internet use by patients. Conclusion: In this brief mail survey to a systematic sample of American oncologists in academic and community practice, respondents reported that a significant proportion of their patients use the Internet to obtain cancer information. Oncologists viewed Internet information as having both positive and negative effects on the clinical encounter. Further research is needed on the effects of patients’ use of the Internet to obtain cancer information involving both patients and oncologists.
Phase II Trial of Autologous Tumor Vaccination, Anti-CD3-Activated Vaccine-Primed Lymphocytes, and Interleukin-2 in Stage IV Renal Cell Cancer
Authors: Chang Alfred E. , Li Qiao , Jiang Guihua , Sayre Donna M. , Braun Thomas M. , Redman Bruce G. 
Published: February 2003

Purpose: Previous preclinical and clinical studies have demonstrated that autologous tumor vaccines can induce relatively specific tumor-reactive T cells in draining lymph nodes. The adoptive transfer of these cells can result in tumor regression.Patients and Methods: Patients with stage IV renal cell cancer (RCC) were vaccinated with irradiated autologous tumor cells admixed with Calmette-Guérin bacillus. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were harvested and the lymphoid cells secondarily activated with anti-CD3 monoclonal antibody and expanded in interleukin 2 (IL-2). The activated cells were subsequently infused intravenously along with the concomitant administration of bolus IL-2 (360,000 U/kg intravenously × 15 doses).Results: Thirty-nine patients were entered onto the study, of whom 34 completed an initial course of cell therapy consisting of a mean (SEM) number of 4.3 (2.2) × 1010VPLN cells. Among subjects who received cell therapy, there were nine responses (four complete responses [CRs] and five partial responses [PRs]), for an overall response rate of 27%. The durations of the CRs were > 48, 45, > 35, and 12 months, and the durations of the PRs were > 63, 48, 15, 12, and 4 months. Cultured tumor cells were available to assess in vitro cytokine release of VPLN cells in 24 subjects. The median cytokine release ratio of interferon gamma (IFNγ) to IL-10 for responders and nonresponders was 992 and 5, respectively, which was significantly different (P = .047).Conclusion: The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFNγ and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.
Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer
Authors: Fuchs Charles S. , Moore Melvin R. , Harker Graydon , Villa Luis , Rinaldi David , Hecht J. Randolph 
Published: February 2003

Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients. Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m2) or once every 3 weeks (350 mg/m2, or 300 mg/m2 in patients who were ≥ 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation). Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively; P = .43), or median time to progression (4.0 v 3.0 months, respectively; P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups. Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.
Nicotine Patch Therapy Based on Smoking Rate Followed by Bupropion for Prevention of Relapse to Smoking
Authors: Hurt Richard D. , Krook James E. , Croghan Ivana T. , Loprinzi Charles L. , Sloan Jeff A. , Novotny Paul J. , Kardinal Carl G. , Knost James A. , Tirona Maria Tria , Addo Ferdinand , Morton Roscoe F. , Michalak John C. , Schaefer Paul L. , Porter Patricia A. , Stella Philip J. 
Published: February 2003

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P = .73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P = .12). Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.
Bidirectional Signaling between the Estrogen Receptor and the Epidermal Growth Factor Receptor
Authors: Levin Ellis R. 
Published: February 2003

AbstractInteractions between the estrogen receptor (ER) and the epidermal growth factor receptor (EGFR) contribute to the biological effects of these binding protein families. EGFR stimulates DNA synthesis and gene transcription in the uterus, related in part to estrogen-independent activation of the nuclear ER. This results from signal transduction enacted by the plasma membrane tyrosine kinase growth factor receptor, leading to 1) phosphorylation and activation of the nuclear ER, and 2) phosphorylation of coregulator proteins. More recently, it has been shown that a pool of ERα resides in or associates with the plasma membrane as a cytoplasmic protein. These ERs utilize the membrane EGFR to rapidly signal through various kinase cascades that influence both transcriptional and nontranscriptional actions of estrogen in breast cancer cells. This is congruent with a general theme of receptor signaling, where membrane G protein-coupled receptors activate tyrosine kinase growth factor receptors (EGFR, IGF-I receptor) that subsequently signal to MAPKs and other pathways. Overall, the bidirectional cross-talk between EGFR and cellular pools of ER contributes to reproductive organ physiology and pathophysiology.
Grain Refinement of Aluminium Alloys by Inoculation
Authors: Greer A.L. , Cooper P.S. , Meredith M.W. , Schneider W. , Schumacher P. , Spittle J.A. , Tronche A. 
Published: February 2003

AbstractA review is given of the studies of aluminium inoculation undertaken within the EU Network “Microstructural Engineering by Solidification Processing” (MEBSP). A wide range of studies of industrial practice of grain refining and of the fundamental mechanisms of nucleation and growth have contributed to improved understanding. Particular advances have been made in understanding the relative performance of different grain refiners.
Der Aufbau von Vancomycin: so macht es die Natur
Authors: Hubbard Brian K. , Walsh Christopher T. 
Published: February 2003

AbstractAntibiotika sind wertvolle Therapeutika im Kampf gegen Infektionen, die durch pathogene Bakterien verursacht werden. Vancomycin ist eine der letzten wirksamen “Waffen” bei lebensbedrohlichen Infektionen durch Gram‐positive Bakterien. Die Regeln, nach denen die Natur die Glycopeptid‐ (Vancomycin) und Lipoglycopeptid‐Antibiotika (Teicoplanin) aufbaut, werden zunehmend geklärt und abgesichert: Zuerst werden Aminosäuren synthetisiert, diese anschließend zusammengebaut und vernetzt. Damit öffnen sich Möglichkeiten, die Synthesestrategien umzuprogrammieren auf der Ebene veränderter Monomere, durch Verschiebungen beim Peptidaufbau und durch verschiedene Enzyme zur Nachbearbeitung des Aglycons.
NMR‐Techniken zum Screening und zur Identifizierung der Bindung von Liganden an Proteinrezeptoren
Authors: Meyer Bernd , Peters Thomas 
Published: February 2003

AbstractErkenntnisse über Bindungsvorgänge zwischen Liganden und Rezeptoren sind der Schlüssel zu einem Verständnis biologischer Prozesse. Seit kurzem ist es möglich, durch neue NMR‐spektroskopische Techniken Protein‐Protein‐ und Protein‐Ligand‐Wechselwirkungen auf atomarer Ebene zu verstehen. Diese Experimente charakterisieren die Bindungsvorgänge entweder von der Seite des Liganden oder von der des Proteins. Idealerweise werden beide Techniken gemeinsam angewendet und liefern dann ein komplettes Bild der Ligandenbindung an einen Rezeptor. Die in diesem Aufsatz vorgestellten Ansätze erlauben das Screening von Verbindungsbibliotheken genauso wie eine detaillierte Charakterisierung von Bindungsepitopen und einzelnen funktionellen Gruppen, die in die Bindungsvorgänge involviert sind. Die Bestimmung der Bindungsstärke und der Bindungskinetik ist ebenso möglich wie die Untersuchung kompetitiver Bindung, allosterischer Effekte oder der Bindung von Liganden an intakte Viren und membranständige Proteine.
Vancomycin Assembly: Nature's Way
Authors: Hubbard Brian K. , Walsh Christopher T. 
Published: February 2003

AbstractAntibiotics are precious resources in the fight to combat bacterial infections caused by pathogenic organisms. Vancomycin is one of the antibiotics of last resort in the treatment of life‐threatening infections by gram‐positive bacteria. The rules by which nature assembles the glycopeptide (vancomycin) and lipoglycopeptide (teicoplanin) antibiotics are becoming elucidated and verified: first amino acids are synthesized, then joined together and cross‐linked. This knowledge opens up approaches for reprogramming strategies at the level of altered monomers, swapped assembly lines, and different post‐assembly tailoring enzymes.
NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors
Authors: Meyer Bernd , Peters Thomas 
Published: February 2003

AbstractBinding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein–protein and protein–ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques. These experiments identify binding events either by looking at the resonance signals of the ligand or the protein. Ideally, both techniques together deliver a complete picture of ligand binding to a receptor. The approaches discussed in this review allow screening of compound libraries as well as a detailed identification of the groups involved in the binding events. Also, characterization of the binding strength and kinetics is possible, competitive binding as well as allosteric effects can be identified, and it has even been possible to identify ligand binding to intact viruses and membrane‐bound proteins.
Antitubercular Isoniazid and Drug Resistance of Mycobacterium tuberculosis — A Review
Authors: Scior Thomas , Meneses Morales Iván , Garcés Eisele Solón Javier , Domeyer David , Laufer Stefan 
Published: February 2003

AbstractIsoniazid is one of the most potent drugs available for tuberculosis treatment. As a pro‐drug it requires activation, which is performed by catalase/peroxidase. The active principle, whose identity has not yet been determined unambiguously, then acts on at least one target molecule, the enoyl‐acyl carrier protein, required for the synthesis of the vital mycolic acids present in the cell wall of the bacterium. Some other targets have been proposed in order to explain the unusual potency of isoniazid; however, the supporting data are still controversial. We thoroughly discuss the action of isoniazid, resistance mechanisms, and the possible active product, which includes an isonicotinic acid‐NADH adduct as well as a meta‐isomer of NADH. Both structures have been probed positively in a 3D modeling analysis.
C16 and C17 Substituted Derivatives of Pregnenolone and Progesterone as Inhibitors of 17α‐Hydroxylase‐C17, 20‐lyase: Synthesis and Biological Evaluation
Authors: Haidar Samer , Hartmann Rolf W. 
Published: February 2003

Abstract17α‐Hydroxylase‐C17, 20‐lyase (P450 17, CYP 17) is a key enzyme in androgen biosynthesis and a target for the treatment of prostate cancer. In order to find novel inhibitors for this enzyme, several compounds bearing different moieties able to complex with the heme iron located in the active site of the enzyme were synthesized. The moieties were introduced into the 16‐position of pregnenolone and progesterone. Their inhibitory activities toward human and rat CYP 17 were determined and compared to the activities of the corresponding 17‐substituted compounds. It became apparent that the 16‐substituted compounds were less active than the parent compounds: they were either moderate or poor inhibitors of the target enzyme. Tested for inhibition of human 5α‐reductase 1 and 2 — a target for the treatment of benign prostatic hyperplasia (BPH) — the title compounds showed some inhibitory activity.
Novel High Energy Intermediate Analogues with Triazasterol‐Related Structures as Inhibitors of Ergosterol Biosynthesis Part I: Synthesis and Antifungal Activity of N‐alkyl‐N′‐(phenethyl‐ and cyclohexenylethyl)guanidines and N2‐Substituted 2‐Imidazolinamines
Authors: Gößnitzer Edith , Malli Roland , Schuster Silvia , Favre Bertrand , Ryder Neil S. 
Published: February 2003

AbstractA series of N‐alkyl‐N′—(phenethyl‐ and cyclohexenylethyl) guanidines and N2‐ and N2, 4‐substituted imidazolin‐2‐amine hydrochlorides with triazasterol‐related structures was designed and synthesized as stable analogues to mimic high energy intermediates of ergosterol biosynthesis. The in vitro antifungal susceptibility tests with a standard panel of pathogenic fungi revealed moderate to strong antimycotic effects of the sixteen prepared compounds, in some cases comparable with the activity observed for itraconazole.
Structure‐Activity Relationship Studies of 1‐Substituted 3‐Dodecanoylindole‐2‐carboxylic Acids as Inhibitors of Cytosolic Phospholipase A2‐Mediated Arachidonic Acid Release in Intact Platelets
Authors: Griessbach Klaus , Klimt Monika , Schulze Elfringhoff Alwine , Lehr Matthias 
Published: February 2003

AbstractA series of 3‐dodecanoylindole‐2‐carboxylic acid derivatives with varied carboxylic acid substituents at the indole 1‐position were synthesized and evaluated for their ability to inhibit arachidonic acid release in human platelets mediated by the cytosolic phospholipase A2. Structure‐activity relationship studies revealed that increasing the polarity of these substituents by the introduction of additional polar groups in the proximity of the carboxylic acid moiety reduced activity. Conformational restriction of the indole‐1‐carboxylic acid substituents in distinct positions as well as extending the length of these residues led to compounds which did not substantially differ in their potencies.
Synthesis and Antiinflammatory Screening of Some Quinazoline and Quinazolyl‐4‐oxoquinazoline Derivatives
Authors: Gineinah Magdy M. , El‐Sherbeny Magda A. , Nasr Magda N. , Maarouf Azza R. 
Published: February 2003

AbstractSynthesis of some new derivatives of 2‐aryl‐4‐oxo‐1‐(4‐quinazolyl)quinazolines is described. Methyl N‐(4‐quinazolyl)anthranilate was allowed to react with phenyl iso(thio)cyanate to give 3‐phenyl‐1‐(4‐quinazolyl)‐1, 2, 3, 4‐tetrahydro‐2, 4‐dioxo‐ and 4‐oxo‐2‐thioxoquinazolines (3a and 3b respectively) Alternatively, anthranilic acid amide derivatives were subjected to cyclization with aromatic aldehydes to give 2‐aryl‐4‐oxo‐1‐(4‐quinazolyl)‐1, 2, 3, 4‐tetrahydroquinazolines 5. On the other hand, 2‐chloro‐4‐(4‐substituted 1‐piperazinyl)quinazoline derivatives were subjected to the same type of reactions at the 2‐position to afford the corresponding quinazoline derivatives 8 and 10 respectively. Furthermore, the acid amide 4b cyclized with acid chlorides to give the corresponding 2‐aryl‐1‐(2‐chloro‐4‐quinazolyl)‐4‐oxo‐1, 4‐dihydroquinazolines 11 from which the triazoloquinazoline derivatives 13 and 15 were synthesized through the intermediate hydrazine derivatives 112Mostof the newly synthesized compounds were tested for their antiinflammatory activities. However, some of the novel compounds were found to exhibit good antiinflammatory potencies.